Cholesterol pp 363-435

Part of the Subcellular Biochemistry book series (SCBI, volume 28) | Cite as

Cholesterol Metabolism and Tumor Cell Proliferation

  • Peter S. Coleman
  • Li-Chuan Chen
  • Laura Sepp-Lorenzino


The functions assumed by free cholesterol in mammalian cells are diverse, ranging from that as a starting substrate for the synthesis of steroid hormones and bile salts to its less specifically understood but critical role as a principal lipid component of every cell membrane. Cholesterol biosynthesis begins with metabolically supplied cytoplasmic acetyl CoA that also serves as the common precursor for de novo fatty acid synthesis, and can be expressed by the reaction: 18 acetyl CoA + 1/2O2 + 10 H+ → cholesterol + 9 CO2 +18 CoA-SH. During the synthesis, the genesis of mevalonic acid (MVA) from 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), catalyzed by HMG-CoA reductase (HMGR), the third and principal rate-controlling enzyme of the pathway, leads to the production of diverse polyisoprenoid intermediates. Metabolism of MVA demonstrates considerable versatility through ensuing branching reactions that yield a host of terpene compounds used in the construction of an assortment of required metabolites [dolichol, ubiquinone(Coenzyme Q), isopentenyl adenine, heme a/a3], in addition to cholesterol itself. This chapter focuses on associations that link cholesterol and mitochondrial citrate export, as well as the metabolism of citrate-derived isoprenoid metabolites en route to cholesterol synthesis, with deregulated cell proliferation (i.e., cancer).


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  1. Adamson, P., Marshall, C. J., Hall, A., and Tilbrook, P. A., 1992, Post-translational modifications of p21 rho proteins, J. Biol. Chem. 267:20033–20038.PubMedGoogle Scholar
  2. Agarwal, S., Corbley, M. J., and Roberts, T. M., 1995, Reconstitution of signal transduction from the membrane to the nucleus in a baculovirus expression system: activation of Raf-1 leads to hyper-modificatio of c-jun and c-fos via multiple pathways, Oncogene 11:427–438.PubMedGoogle Scholar
  3. Akopyan, T. N., Couedel, Y., Orlowski, M., Fournie-Zaluski, M. C., and Roques, B. P., 1994, Proteolytic processing of famesylated peptides: assay and partial purification from pig brain membranes of an endopeptidase which has the characteristics of E.C., Biochem. Biophys. Res. Com-mun. 198:787–794.CrossRefGoogle Scholar
  4. Alberts, A., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H., Harris, E., Patchett, A., Monaghan, R., Currie, S., Stapley, E., Albers-Schonberg, G., Hensens, O., Hirshfield, J., Hoogsteen, K., Liesch, J., and Springer, J., 1980, Mevinolin: a highly potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase and a cholesterol-lowering agent, Proc. Natl. Acad. Sci. USA 77:3957–3961.PubMedCrossRefGoogle Scholar
  5. Appelkvist, E. L., Reinhart, M., Fischer, R., Billheimer, J., and Daliner, G., 1990, Presence of individual enzymes of cholesterol biosynthesis in rat liver peroxisomes, Arch. Biochem. Biophys. 282: 318–325.PubMedCrossRefGoogle Scholar
  6. Appelkvist, E. L., Grünler, J., and Dallner, G., 1995, Isoprenoid biosynthesis in peroxisomes, FASEB J. 9:A1312.Google Scholar
  7. Armstrong, S. A., Hannah, V. C., Goldstein, J. L., and Brown, M. S., 1995, CAAX geranylger-anyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB, J. Biol. Chem. 270:7864–7868.PubMedCrossRefGoogle Scholar
  8. Aronheim, A., Engelberg, D., Li, N., Al-Alawi, N., Schlessinger, J., and Karin, M., 1994, Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway, Cell 78:949–961.PubMedCrossRefGoogle Scholar
  9. Azarnoff, D. L., Tucker, D. R., and Barr, G. A., 1965, Studies with ethyl chlorophenoxyisobutyrate (Clofibrate), Metabolism 14:959–965.PubMedCrossRefGoogle Scholar
  10. Azrolan, N. I., and Coleman, P. S., 1989, A discoordinate increase in the cellular amount of 3-hydroxy-3-methylglutaryl-CoA reductase results in the loss of rate-limiting control over cholesterogenesis in a tumor cell-free system, Biochem. J. 258:421–425.PubMedGoogle Scholar
  11. Barbacid, M., 1987, ras genes, Annu. Rev. Biochem. 56:779–827.PubMedCrossRefGoogle Scholar
  12. Biardi, L., Sreedhar, A., Zokaei, A., Vartak, N. B., Bozeat, R. L., Shackelford, J. E., Keller, G. A., and Krisans, S. K., 1994, Mevalonate kinase is predominantly localized in peroxisomes and is defective in patients with peroxisome deficiency disorders, J. Biol. Chem. 269:1197–1205.PubMedGoogle Scholar
  13. Bilger, B., 1995, Forever young, The Sciences 35:26–30.Google Scholar
  14. Bishop, J. M., 1991, Molecular themes in oncogenesis, Cell 64:235–248.PubMedCrossRefGoogle Scholar
  15. Black, S. D., 1992, Development of hydrophobicity parameters for prenylated proteins, Biochem. Biophys. Res. Commun. 186:1437–1442.PubMedCrossRefGoogle Scholar
  16. Blenis, J., 1993, Signal transduction via MAP kinases: proceed at your own RSK, Proc. Natl. Acad. Sci. USA 90:5889–5892.PubMedCrossRefGoogle Scholar
  17. Blouin, A., Bolender, R. P., and Weibel, E. R., 1977, Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma, J. Cell Biol. 72: 441–455.PubMedCrossRefGoogle Scholar
  18. Boctor, A. M., and Bystryn, J.-C, 1982, Degradation of tumor-associated antigens shed by human melanoma cells in culture, Cancer Res. 42:2121–2125.PubMedGoogle Scholar
  19. Boguski, M. S., and McCormick, F., 1993, Proteins regulating Ras and its relatives, Nature 366: 643–654.PubMedCrossRefGoogle Scholar
  20. Bradfute, D. L., and Simoni, R. D., 1994, Non-sterol compounds that regulate cholesterogenesis: analogues of farnesyl pyrophosphate reduce 3-hydroxy-3-methylglutaryl-coenzyme A reductase levels, J. Biol. Chem. 269:6645–6650.PubMedGoogle Scholar
  21. Braun, P.E., De Angelis, D., Shtybel, W. W., and Bernier, L., 1991, Isoprenoid modification permits 2’,3’-cyclic nucleotide 3′-phosphodiesterase to bind to membranes, J. Neurosci. Res. 30:540–544.PubMedCrossRefGoogle Scholar
  22. Brenneman, D. E., Mathur, S. N., and Spector, A. A., 1975, Characterization of the hyperlipidemia in mice bearing the Ehrlich ascites tumor, Eur. J. Cancer 11:225–230.PubMedCrossRefGoogle Scholar
  23. Brown, M. S., and Goldstein, J. L., 1980, Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth, J. Lipid Res. 21:505–517.PubMedGoogle Scholar
  24. Brown, M. S., Faust, J. R., Goldstein, J. L., Kaneko, I., and Endo, A., 1978, Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase, J. Biol. Chem. 253:1121–1128.PubMedGoogle Scholar
  25. Brown, M. S., Goldstein, J. L., Paris, K. J., Burnier, J. P., and Masters, J. C., Jr., 1992, Tetrapeptide inhibitors of protein:farnesyltransferase: amino-terminal substitution in phenylalanine-containing tetrapeptides restores farnesylation, Proc. Natl. Acad. Sci. USA 89:8313–8316.PubMedCrossRefGoogle Scholar
  26. Bruenger, E., and Rilling, H. C., 1986, Prenylated proteins from kidney, Biochem. Biophys. Res. Commun. 139:209–214.PubMedCrossRefGoogle Scholar
  27. Bruscalupi, G., Castellano, F., Sacco, S., and Trentalance, A., 1994, Prenylated proteins in regenerating rat liver, Biochem. Biophys. Res. Commun. 200:1713–1720.PubMedCrossRefGoogle Scholar
  28. Bryla, J., 1981, Inhibitors of mitochondrial anion transport, Inhibitors of Mitochondrial Function (M. Erecinska and D. F. Wilson, eds.), pp. 211–259, Pergamon Press, New York.Google Scholar
  29. Buchwald, H., 1992, Cholesterol inhibition, cancer, and chemotherapy, Lancet 339:1154–1156.PubMedCrossRefGoogle Scholar
  30. Bukhtiyarov, Y. E., Omer, C. A., and Allen, C. M., 1995, Photoreactive analogues of prenyl diphosphates as inhibitors and probes of human protein farnesyltransferase and geranylgeranyltrans-ferase type I, J. Biol. Chem. 270:19035–19040.PubMedCrossRefGoogle Scholar
  31. Call, T. G., Stenson, M. J., and Witzig, T. E., 1994, Effects of phenylacetate on cells from patients with B-chronic lymphocytic leukemia, Leukemia Lymphoma 14:145–149.PubMedCrossRefGoogle Scholar
  32. Carboni, J. M., Yan, N., Cox, A. D., Bustelo, X., Graham, S. M., Lynch, M. J., Weinmann, R., Seizinger, B. R., Der, C. J., Barbacid, M., and Manne, V., 1995, Farnesyltransferase inhibitors are inhibitors of Ras but not R-Ras2/TC21 transformation, Oncogene 10:1905–1913.PubMedGoogle Scholar
  33. Casey, P. J., 1995, Protein lipidation in cell signaling, Science 268:221–225.PubMedCrossRefGoogle Scholar
  34. Casey, P. J., and Seabra, M. C., 1996, Protein Prenyltransferases, J. Biol. Chem. 271: 5289–5292.PubMedCrossRefGoogle Scholar
  35. Castillo, M., Burgos, C., Rodriques-Vico, R., Zafra, M. F., and Garcia-Peregrin, E., 1990, Effects of Clofibrate on the main regulatory enzymes of cholesterogenesis, Life Sci. 46:397–403.PubMedCrossRefGoogle Scholar
  36. Castillo, M., Iglesias, J., Zafra, M. F., and Garcia-Peregrin, E., 1991a, Inhibition of chick brain cho-lesterogenic enzymes by phenyl and phenolic derivatives of phenylalanine, Neurochem. Int. 18: 171–174.PubMedCrossRefGoogle Scholar
  37. Castillo, M., Martinez-Cayuela, M., Zafra, M. F., and Garcia-Peregrin, E., 1991b, Effect of phenylalanine derivatives on the main regulatory enzymes of hepatic cholesterogenesis, Mol. Cell. Biochem. 105:21–25.PubMedCrossRefGoogle Scholar
  38. Chan, A. M.-L., Miki, T., Meyers, K., and Aaronson, S. A., 1994, A human oncogene of the RAS superfamily unmasked by expression cDNA cloning, Proc. Natl. Acad. Sci. USA 91:7558–7562.PubMedCrossRefGoogle Scholar
  39. Chazotte, B., and Hackenbrock, C. R., 1988, The multicollisional, obstructed, long-range diffusional nature of mitochondrial electron transport, J. Biol. Chem. 263:14359–14367.PubMedGoogle Scholar
  40. Chazotte, B., and Hackenbrock, C.R., 1991, Modulation and analysis of structure and function of the inner mitochondrial membrane through the application of phospholipid enrichment and membrane fusion techniques, Membrane Fusion (J. Wilschut and D. Hoekstra, eds.), pp. 803–844, Marcel Dekker, New York.Google Scholar
  41. Chen, H., Born, E., Mathur, S. N., and Field, F. J., 1993, Cholesterol and sphingomyelin syntheses are regulated independently in cultured intestinal cells, CaCo-2: role of membrane cholesterol and sphingomyelin content, J. Lipid Res. 34:2159–2167.PubMedGoogle Scholar
  42. Chen, H. W., 1984, Role of cholesterol metabolism in cell growth, Fed. Proc. 43:126–130.PubMedGoogle Scholar
  43. Chen, H. W., Heiniger, H.-J. and Kandutsch, A. A., 1975, Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes, Proc. Natl. Acad. Sci. USA 72: 1950–1954.PubMedCrossRefGoogle Scholar
  44. Chen, H. W., Kandutsch, A. A., and Heiniger, H.-J., 1978, The role of cholesterol in malignancy, Prog. Exp. Tumor Res. (D. F. H. Wallach, ed.), pp. 275–316, S. Karger, Basel.Google Scholar
  45. Chen, W.-J., Andres, D., Goldstein, J. L., Russell, D., and Brown, M., 1991, cDNA cloning and expression of the peptide-binding subunit of rat p21ras farnesyltransferase, the counterpart of yeast DPR1/RAM1, Cell 66:327–334.PubMedCrossRefGoogle Scholar
  46. Chen, W.-J., Moomaw, J. F., Overton, L., Kost, T. A., and Casey, P., 1993, High level expression of mammalian protein farnesyltransferase in a baculovirus system, J. Biol. Chem. 268: 9675–9680.PubMedGoogle Scholar
  47. Chin, C. J., Luskey, K. L., Anderson, R. G. W., Faust, J. R., Goldstein, J. L., and Brown, M. S., 1982, Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Proc. Natl. Acad. Sci. USA 79:1185–1189.PubMedCrossRefGoogle Scholar
  48. Cinatl, J., Cinatl, J., Mainke, M., Weissflog, A., Rabenau, H., Kornhuber, B., and Doerr, H. W., 1993, In vitro differentiation of human neuroblastoma cells by sodium phenylacetate, Cancer Lett. 70:15–24.PubMedCrossRefGoogle Scholar
  49. Cinatl, J., Cinatl, J., Herneiz, P., Rabenau, H., Novak, M., Benda, R., Giimbel, H., Kornhuber, B., and Doerr, H. W., 1994, Induction of myogenic differentiation in a human rhabdomyosarcoma cell line by phenylacetate, Cancer Lett. 78:41–48.PubMedCrossRefGoogle Scholar
  50. Clarke, S., 1992, Protein isoprenylation and methylation at carboxy-terminal cysteine residues, Annu. Rev. Biochem. 61:355–386.PubMedCrossRefGoogle Scholar
  51. Clarke, S., Vogel, J., Deschenes, R., and Stock, J., 1988, Post-translational modification of the H-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferase, Proc. Natl. Acad. Sci. USA 85:4643–4647.PubMedCrossRefGoogle Scholar
  52. Clegg, R. J., Middleton, B., Bell, G. D., and White, D. A., 1980, Inhibition of hepatic cholesterol synthesis and 3-hyroxy-3-methylglutaryl coenzyme A reductase by mono and bicyclic monoterpenes administered in vivo, Biochem. Pharmacol. 29:2125–2127.PubMedCrossRefGoogle Scholar
  53. Clegg, R. J., Middleton, B., Bell, G. D., and White, D. A., 1982, The mechanism of cyclic monoter-pene inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase in vivo in the rat, J. Biol. Chem. 257:2294–2299.PubMedGoogle Scholar
  54. Cohen, B. I., Raicht, R. F., Shefer, S., and Mosbach, E. H., 1974, Effects of Clofibrate on sterol metabolism in the rat, Biochim. Biophys. Acta 369:79–85.PubMedCrossRefGoogle Scholar
  55. Cohen, L. H., Valentijn, A. R. P. M., Roodenburg, L., van Leeuwen, R. E. W., Huisman, R. H., Lutz, R. J., van der Marel, G. A., and van Boom, J. H., 1995, Different analogs of farnesyl pyrophosphate inhibit squalene synthase and protein:farnesyltransferase to different extents, Biochem. Pharmacol. 49:839–845.PubMedCrossRefGoogle Scholar
  56. Coleman, P. S., 1986a, Membrane cholesterol and tumor bioenergetics, Ann. NY Acad. Sci. 488: 451–467.PubMedCrossRefGoogle Scholar
  57. Coleman, P. S., 1986b, The mitochondrial citrate transport carrier and the role of deregulated choles-terogenesis in tumor cell proliferation, EBEC Reports 4:11.Google Scholar
  58. Coleman, P. S., 1991, Deterministic coupling between cellular bioenergetics, cholesterol synthesis, cell proliferation and cancer, Chemical Carcinogenesis 2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 265–288, Springer Science+Business Media New York.Google Scholar
  59. Coleman, P. S., and Lavietes, B. B., 1981, Membrane cholesterol, tumorigenesis, and the biochemical phenotype of neoplasia, CRC Crit. Rev. Biochem. 11:341–393.PubMedGoogle Scholar
  60. Coleman, P. S., and Sepp-Lorenzino, L., 1990, The role of the cholesterol synthesis pathway during tumor cell proliferation, Adv. Cholesterol Res. (M. Esfaham and J. Swaney, eds.), pp. 201–270, Telford Press, NJ.Google Scholar
  61. Coleman, P. S., Lavietes, B., Born, R., and Weg, A., 1978, Cholesterol enrichment of normal mitochondria in vitro: a model system with properties of hepatoma mitochondria, Biochem. Biophys. Res. Commun. 84:202–207.PubMedCrossRefGoogle Scholar
  62. Corsini, A., Verri, D., Raiteri, M., Quarato, M., Paoletti, R., and Fumagalli, R., 1995, Effects of 26-aminocholesterol, 27-hydroxycholesterol and 25-hydroxycholesterol on proliferation and cholesterol homeostasis in arterial monocytes, Arterio. Throm. Vasc. Biol. 15:420–428.CrossRefGoogle Scholar
  63. Cox, A. D., and Der, C. J., 1992, The ras/cholesterol connection: implications for ras oncogenicity, Crit. Rev. Oncogen. 3:365–400.Google Scholar
  64. Cox, D. C., Comai, K., and Goldstein, A. L., 1988, Effects of cholesterol and 25-hydroxycholesterol on smooth muscle cell and endothelial cell growth, Lipids 23:85–88.PubMedCrossRefGoogle Scholar
  65. Cox, A. D., Garcia, A. M., Westwick, J. K., Kowalczyk, J. J., Lewis, M. D., Brenner, D. A., and Der, C. J., 1994, The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristoylated, oncogenic ras signaling and transformation, J. Biol. Chem. 269:19203–19206.PubMedGoogle Scholar
  66. Crowell, P. L., and Gould, M. N., 1994, Chemoprevention and therapy of cancer by d-limonene, Crit. Rev. Oncogenesis 5:1–22.PubMedCrossRefGoogle Scholar
  67. Crowell, P. L., Chang, R., Ren, Z., Elson, C., and Gould, M., 1991, Selective inhibition of isoprenylation of 21-26-kDa proteins by the anticarcinogen d-limonene and its metabolites, J. Biol. Chem. 266:17679–17685.PubMedGoogle Scholar
  68. Crowell, P. L., Lin, S., Vedejs, E., and Gould, M. N., 1992, Identification of circulating metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth, Cancer Chemoth. Pharmacol. 31:205–212.CrossRefGoogle Scholar
  69. Crowell, P. L., Ren, Z., Lin, S., Vedejs, E., and Gould, M. N., 1994, Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation, Biochem. Pharmacol 47:1405–1415.PubMedCrossRefGoogle Scholar
  70. Cuthbert, J. A., and Lipsky, P. E., 1991, Negative regulation of cell proliferation by mevalonate or one of the mevalonate phosphates, J. Biol. Chem. 266:17966–17971.PubMedGoogle Scholar
  71. Cuthbert, J. A., and Lipsky, P. E., 1995, Suppression of the proliferation of ras-transformed cells by fluoromevalonate, an inhibitor of mevalonate metabolism, Cancer Res. 55:1732–1740.PubMedGoogle Scholar
  72. Dalton, M. B., Fantle, K. S., Bechtold, H. A., DeMaio, L., Evans, R. M., Krystosek, A., and Sinensky, M., 1995, The farnesyl protein transferase inhibitor BZA-5B blocks farnesylation of nuclear lamins and p21ras but does not affect their function or localization, Cancer Res. 55: 3295–3304.PubMedGoogle Scholar
  73. Das, N. P., and Allen, C. M., 1991, Inhibition of farnesyl transferases from malignant and non-malignant cultured human lymphocytes by prenyl substrate analogues, Biochem. Biophys. Res. Commun. 181:729–735.PubMedCrossRefGoogle Scholar
  74. Daum, G., 1985, Lipids of mitochondria, Biochim. Biophys. Acta 822:1–42.PubMedCrossRefGoogle Scholar
  75. Davis, R. J., 1993, The mitogen-activated protein kinase signal transduction pathway, J. Biol. Chem. 268:14553–14556.PubMedGoogle Scholar
  76. DeClue, J. E., Vass, W. C., Papageorge, A. G., Lowy, D. R., and Willumsen, B. M., 1991, Inhibition of cell growth by lovastatin is independent of ras function, Cancer Res. 51:712–717.PubMedGoogle Scholar
  77. Dessi, S., Batetta, B., Anchisi, C., Pani, P., and Costelli, P., 1992, Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130), Br. J. Cancer 66:787–793.PubMedCrossRefGoogle Scholar
  78. Dietschy, J. M., and Siperstein, M. D., 1967, Effect of cholesterol feeding and fasting on sterol synthesis in seventeen tissues of the rat, J. Lipid Res. 8:97–104.PubMedGoogle Scholar
  79. Downward, J., 1990, The ras superfamily of small GTP-binding proteins, Trends Biochem. Sci. 15: 469–472.PubMedCrossRefGoogle Scholar
  80. Doyle, J., Kabakoff, B., and Kandutsch, A. A., 1991, Dolichyl phosphate as a regulator of cell growth, Chemical Carcinogenesis-2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 289–297, Springer Science+Business Media New York.Google Scholar
  81. Echegoyen, S., Oliva, E. B., Sepulveda, J., Diaz-Zagoya, J. C., Espinosa-Garcia, M. T., Pardo, J. P., and Martinez, F., 1993, Cholesterol increase in mitochondria: its effect on inner-membrane functions, submitochondrial localization and ultrastructure morphology, Biochem. J. 289: 703–708.PubMedGoogle Scholar
  82. Edwards, P. A., Lan, S.-F., and Fogelman, A. M., 1984, High density lipoproteins and lecithin dispersions increase the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by increasing the rate of synthesis and decreasing the rate of degradation of the enzyme, J. Biol. Chem. 259: 8190–8194.PubMedGoogle Scholar
  83. Elson, C. E., and Yu, S. G., 1994, The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables, J. Nutrit. 124:607–614.PubMedGoogle Scholar
  84. Endo, A., 1992, The discovery and development of HMG-CoA reductase inhibitors, J. Lipid Res. 33:1569–1582.PubMedGoogle Scholar
  85. Endo, A., Kuroda, M., and Tanazawa, K., 1976, Competitive inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by ML-236A and ML-236B, fungal metabolites having hypocholesterolemic activity, FEBS Lett. 72:323–325.PubMedCrossRefGoogle Scholar
  86. Ericsson, J., Appelkvist, E. L., Runquist, M., and Dallner, G., 1993, Biosynthesis of dolichol and cholesterol in rat liver peroxisomes, Biochimie 75:167–173.PubMedCrossRefGoogle Scholar
  87. Fairbanks, K. P., Witte, L. D., and Goodman, D. S., 1984, Relationship between mevalonate and mitogenesis in human fibroblasts stimulated with platelet-derived growth factor, J. Biol. Chem. 259:1546–1551.PubMedGoogle Scholar
  88. Fairbanks, K. P,Barbu, V. D., Witte, L. D., Weinstein, I. B., and Goodman, D. S., 1986, Effects of me vi-nolin and mevalonate on cell growth in several transformed cell lines, J. Cell. Physiol 127:216–222.PubMedCrossRefGoogle Scholar
  89. Farias, R. N., Bloj, B., Morero, R. D., Sineriz, F., and Trucco, R. E., 1975, Regulation of allosteric membrane-bound enzymes through changes in membrane lipid composition, Biochim. Biophys. Acta 415:231–254.PubMedCrossRefGoogle Scholar
  90. Farnsworth, C. C., Gelb, M. H., and Glomset, J. A., 1990, Identification of geranylgeranyl-modified proteins in HeLa cells, Science 247:320–322.PubMedCrossRefGoogle Scholar
  91. Farnsworth, C. C., Yamane, H., Gelb, M., and Glomset, J. A., 1990, A 23 kDa GTP-binding protein from bovine brain membranes is geranylgeranylated, FASEB J. 4:870a.Google Scholar
  92. Faust, J. R., Lusky, K. L., Chin, D. J., Goldstein, J. L., and Brown, M. S., 1982, Regulation of synthesis and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by low density lipoprotein and 25-hydroxycholesterol in UT-1 cells, Proc. Natl Acad. Sci. USA 79:5205–5209.PubMedCrossRefGoogle Scholar
  93. Feo, F., Canuto, R. A., Bertone, G., Garcea, R., and Pani, P., 1973, Cholesterol and phospholipid composition of mitochondria and microsomes isolated from Morris hepatoma 5123 and rat liver, FEBS Lett. 33:229–232.PubMedCrossRefGoogle Scholar
  94. Feo, F., Canuto, R.A., Garcea, R., and Gabriel, L., 1975, Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver, and hepatomas AH-130, 3924A and 5123, Biochim. Biophys. Acta 413:116–134.PubMedCrossRefGoogle Scholar
  95. Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlman, T., Noonan, D. J., Burke, L. T., McMorris, T., Lamph, W. W., Evans, R. M., and Weinberger, C., 1995, Identification of a nuclear receptor that is activated by farnesol metabolites, Cell 81:687–693.PubMedCrossRefGoogle Scholar
  96. Garcia, A. M., Rowell, C., Ackermann, K., Kowalczyk, J. J., and Lewis, M. D., 1993, Pep-tidomimetic inhibitors of Ras farnesylation and function in whole cells, J. Biol. Chem. 268:18415–18418.PubMedGoogle Scholar
  97. Gelb, M. H., Tamanoi, F., Yokoyama, K., Ghomashchi, E, Esson, K., and Gould, M. N., 1995, The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol, Cancer Lett. 91:169–175.PubMedCrossRefGoogle Scholar
  98. Giannakouros, T., and Magee, A. I., 1993, Protein prenylation and associated modifications, Lipid Modification of Proteins (M. J. Schlesinger, eds.), pp. 136–162, CRC Press, Boca Raton, Florida.Google Scholar
  99. Gibbs, J. B., 1991, Ras C-terminal processing enzymes-new drug targets? Cell 65:1–4.PubMedCrossRefGoogle Scholar
  100. Gibbs, J. B., 1992, Pharmacologic probes of Ras function, Cancer Biol. 3:383–390.Google Scholar
  101. Gibbs, J. B., Pompliano, D. L., Mosser, S.D., Rands, E., Lingham, R. B., Singh, S. B., Scolnick, E. M., Kohl, N. E., and Oliff, A., 1993, Selective inhibition of farnesyl-protein transferase blocks processing in vivo, J. Biol. Chem. 268:7617–7620.PubMedGoogle Scholar
  102. Gibbs, J. B., Oliff, A., and Kohl, N. E., 1994, Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic, Cell 77:175–178.PubMedCrossRefGoogle Scholar
  103. Glomset, J. A., Gelb, M. H., and Farnsworth, C. C., 1990, Prenyl proteins in eukaryotic cells: a new type of membrane anchor, Trends Biochem. Sci. 15:139–142.PubMedCrossRefGoogle Scholar
  104. Glomset, J., Gelb, M., and Farnsworth, C., 1992, Geranylgeranylated proteins, Biochem. Soc. Trans. 20:479–484.PubMedGoogle Scholar
  105. Goldfisher, S., and Reddy, J. K., 1984, Peroxisomes (microbodies) in cell pathology, Intl. Rev. Exp. Pathol 26:45–84.Google Scholar
  106. Goldstein, J. L., and Brown, M. S., 1990, Regulation of the mevalonate pathway, Nature 343:425–430.PubMedCrossRefGoogle Scholar
  107. Goldstein, J. L., Brown, M. S., Stradley, S. J., Reiss, Y., and Gierasch, L. M., 1991, Nonfarnesylated tetrapeptide inhibitors of protein farnesyltransferase, J. Biol. Chem. 266:15575–15578.PubMedGoogle Scholar
  108. Goodman, L. E., Perou, C. M., Fujiama, A., and Tamanoi, F., 1988, Structure and expression of yeast DPR1, a gene essential for the processing and intracellular localization of ras proteins, Yeast 4: 271–281.PubMedCrossRefGoogle Scholar
  109. Gould, M. N., Moore, C. J., Zhang, R., Wang, B., Kennan, W. S., and Haag, J. D., 1994, Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras, Cancer Res. 54:3540–3543.PubMedGoogle Scholar
  110. Graham, J. M., and Green, C., 1970, The properties of mitochondria enriched in vitro with cholesterol, Eur. J. Biochem. 12:58–66.PubMedCrossRefGoogle Scholar
  111. Graham, S. L., deSolms, S. J., Giuliani, E. A., Kohl, N. E., Mosser, S. D., Oliff, A. I., Pompliano, D. L., Rands, E., Breslin, M. J., Deana, A. A., Garsky, V. M., Scholz, T. H., Gibbs, J. B., and Smith, R. L., 1994, Pseudopeptide inhibitors of Ras farnesyl-protein transferase, J. Med. Chem. 37:725–732.PubMedCrossRefGoogle Scholar
  112. Grünler, J., Ericsson, J., and Dallner, G., 1994, Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins, Biochim. Biophys. Acta 1212:259–277.PubMedCrossRefGoogle Scholar
  113. Guidotti, G., 1972, Membrane proteins, Annu. Rev. Biochem. 41:731–752.PubMedCrossRefGoogle Scholar
  114. Gupte, S., Wu, E.-S., Hoechli, L., Hoechli, M., Jacobson, K., Sowers, A. E., and Hackenbrock, C. R., 1984, Relationship between lateral diffusion, collisional frequency, and electron transfer of mitochondrial inner membrane oxidation-reduction components, Proc. Natl. Acad. Sci. USA 81: 2606–2610.PubMedCrossRefGoogle Scholar
  115. Guthrie, N., Nesaretnam, K., Chambers, A. F., and Carroll, K. K., 1993, Inhibition of breast cancer cell growth by tocotrienols, FASEB J. 7:A7.Google Scholar
  116. Gutierrez, L., Magee, A., Marshall, C., and Hancock, J., 1989, Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis, EMBO J. 8:1093–1098.Google Scholar
  117. Haag, J. D., Lindstrom, M. J., and Gould, M. N., 1992, Limonene-induced regression of mammary carcinomas, Cancer Res. 52:4021–4026.PubMedGoogle Scholar
  118. Habenicht, A. J. R., Glomset, J. A., and Ross, R., 1980, Relation of cholesterol and mevalonic acid to the cell cycle in smooth muscle and Swiss 3T3 cells stimulated to divide with platelet-derived growth factor, J. Biol. Chem. 255:5134–5140.PubMedGoogle Scholar
  119. Hackenbrock, C. R., 1981, Lateral diffusion and electron transfer in the mitochondrial inner membrane, Trends Biochem. Sci. 6:151–154.CrossRefGoogle Scholar
  120. Hackenbrock, C. R., Schneider, H., Lemasters, J. J., and Hochli, M., 1980, Diffusional activity of redox components related to electron transfer in the mitochondrial energy transducing membrane, EBEC Reports 1:23–24.Google Scholar
  121. Haines, T. H., 1993, Water transport across biological membranes, FEBS Lett. 346:115–122.CrossRefGoogle Scholar
  122. Hall, A., 1990, The cellular functions of small GTP-binding proteins, Science 249:635–640.PubMedCrossRefGoogle Scholar
  123. Hall, A., 1994, A biochemical function for Ras-at last, Science 264:1413–1414.PubMedCrossRefGoogle Scholar
  124. Hamilton, R. L., Wong, J. S., Guo, L. S., Krisans, S. K., and Havel, R. J., 1990, Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryo-thin sections, J. Lipid Res. 31: 1589–1604.PubMedGoogle Scholar
  125. Hancock, J. F., Magee, A. I., Childs, J. E., and Marshall, C. J., 1989, All ras proteins are polyiso-prenylated but only some are palmitoylated, Cell 57:1167–1177.PubMedCrossRefGoogle Scholar
  126. Hancock, J. F., Paterson, H., and Marshall, C. J., 1990, A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21-ras to the plasma membrane, Cell 63: 133–139.PubMedCrossRefGoogle Scholar
  127. Hancock, J. F., Cadwallader, K., and Marshall, C. J., 1991, Methylation and proteolysis are essential for efficient membrane binding of prenylated p21(K-ras(B)), EMBO J. 10:641–646.Google Scholar
  128. Hara, M., Akasaka, K., Akinaga, S., Okabe, M., Nakano, H., Gomez, R., Wood, D., Uh, M., and Tamanoi, F., 1993, Identification of Ras farnesyltransferase inhibitors by microbial screening, Proc. Natl Acad. Sci. USA 90:2281–2285.PubMedCrossRefGoogle Scholar
  129. Haiti, F.-U., Pfanner, N., Nicholson, D. W., and Neupert, W., 1989, Mitochondrial protein import, Biochim. Biophys. Acta 988:1–45.CrossRefGoogle Scholar
  130. Hashimoto, F., Ishikawa, T., Hamada, S., and Hayashi, H., 1995, Effect of gemfibrozil on lipid biosynthesis from acetyl-CoA derived from peroxisomal β-oxidation, Biochem. Pharmacol. 49: 1213–1221.PubMedCrossRefGoogle Scholar
  131. Hayashi, H., and Miwa, A., 1989, The role of peroxisomal fatty acyl CoA β-oxidation in bile acid synthesis, Arch. Biochem. Biophys. 274:582–589.PubMedCrossRefGoogle Scholar
  132. Hiatt, R. A., and Fireman, B. H., 1986, Serum cholesterol and the incidence of cancer in a large cohort, J. Chronic Dis. 39:861–870.PubMedCrossRefGoogle Scholar
  133. Hohl, R. J., and Lewis, K., 1995, Differential effects of monoterpenes and lovastatin on RAS processing, J. Biol. Chem. 270:17508–17512.PubMedCrossRefGoogle Scholar
  134. Hornbeck, P., Huang, K.-R, and Paul, W., 1988, Lamin B is rapidly phosphorylated in lymphocytes after activation of protein kinase C., Proc. Natl. Acad. Sci. USA 85:2279–2283.PubMedCrossRefGoogle Scholar
  135. Hudgins, W. R., Shack, S., Myers, C. E., and Samid, D., 1995, Antitumor activity of phenylacetate and derivatives: Correlation with lipophilicity and inhibition of protein prenylation, Biochem. Pharmacol. 50:1273–1279.PubMedCrossRefGoogle Scholar
  136. Isserman, I., and Green, S., 1990, Activation of a member of the steroid hormone receptor super-family by peroxisome proliferators, Nature 347:645–650.CrossRefGoogle Scholar
  137. Jain, M. K., 1975, Role of cholesterol in biomembranes and related systems, in: Curr. Topics Memb. Transport (F. Bronner and A. Kleinzeller, eds.), pp. 1–84, Academic Press, NY.Google Scholar
  138. Jain, M. K., and White, H. B., III, 1977, Long-range order in biomembranes, Adv. Lipid Res. 15:1–60.PubMedGoogle Scholar
  139. Jakobisiak, M., Bruno, S., Skierski, J., and Darzynkiewicz, Z., 1991, Cell cycle-specific effects of lovastatin, Proc. Natl. Acad. Sci. USA 88:3628–3632.PubMedCrossRefGoogle Scholar
  140. James, G., Goldstein, J. L. and Brown, M. S., 1996, Resistance of K-RasBV12 proteins to farnesyl-transferase inhibitors in Rat 1 cells, Proc. Natl. Acad. Sci. USA 93: 4454–4458.PubMedCrossRefGoogle Scholar
  141. James, G. L., Goldstein, J. L., Brown, M. S., Rawson, T. E., Somers, T. C., McDowell, R. S., Crowley, C. W., Lucas, B. K., Levinson, A. D., and Marsters, J. C. J., 1993, Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells, Science 260:1937–1942.PubMedCrossRefGoogle Scholar
  142. James, G. L., Brown, M. S., Cobb, M. H., and Goldstein, J. L., 1994, Benzodiazepine peptidomimetic BZA-5B interrupts the MAP kinase activation pathway in H-ras transformed Rat-1 cells, but not in untransformed cells, J. Biol. Chem. 269:21105–21114.Google Scholar
  143. James, G. L., Goldstein, J. L., Pathak, R. K., Anderson, R. G. W., and Brown, M. S., 1994, PxF, a prenylated protein of peroxisomes, J. Biol. Chem. 269:14182–14190.PubMedGoogle Scholar
  144. James, G. L., Goldstein, J. L. and Brown, M. S., 1995, Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistence to benzodiazepine peptidomimetic in vitro J. Biol. Chem. 270: 6221–6226.PubMedCrossRefGoogle Scholar
  145. Kandutsch, A. A., and Chen, H. W., 1977, Consequences of blocked sterol synthesis in culture cells: DNA synthesis and membrane composition, J. Biol. Chem. 252:409–415.PubMedGoogle Scholar
  146. Kandutsch, A. A., and Hancock, R. L., 1971, Regulation of the rate of sterol synthesis and the level of β-hydroxy-β-methyglutaryl coenzyme A reductase activity in mouse liver and hepatomas, Cancer Res. 31:1396–1400.PubMedGoogle Scholar
  147. Kandutsch, A. A., Heiniger, H.-J., and Chen, H. W., 1977, Effects of 25-hydroxycholesterol and 7-ketocholesterol inhibitors, Biochim. Biophys. Acta 486:260–272.PubMedCrossRefGoogle Scholar
  148. Kaplan, R. S., 1996, Mitochondrial transport processes, in: Molecular Biology of Membrane Transport Disorders (S. G. Schultz, T. Andreoli, A. Brown et al., eds.), pp. 277–302, Plenum Press, NY.CrossRefGoogle Scholar
  149. Kaplan, R. S., Mayor, J. A., Johnston, N., and Oliveira, D. L., 1990, Purification and characterization of the reconstitutively active tricarboxylate transporter from rat liver, J. Biol. Chem. 265: 13379–13385.PubMedGoogle Scholar
  150. Kaplan, R. S., and Mayor, J. A., 1993, Structure, function and regulation of the tricarboxylate transport protein from rat liver mitochondria, J. Bioener. Biomemb. 25:503–514.CrossRefGoogle Scholar
  151. Kaplan, R. S., Mayor, J. A., and Wood, D. O., 1993, The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins, J. Biol. Chem. 268:13682–13690.PubMedGoogle Scholar
  152. Kaplan, R. S., Parlo, R. A., and Coleman, P. S., 1986, Measurement of citrate transport in tumor mitochondria, Meth. Enzymol. 125:671–691.PubMedCrossRefGoogle Scholar
  153. Kaplan, R. S., Morris, H. P., and Coleman, P. S., 1982, Kinetic characteristics of citrate influx and efflux with mitochondria from Morris hepatomas 3924A and 16, Cancer Res. 42:4399–4407.PubMedGoogle Scholar
  154. Kaschnitz, R. M., Morris, H. P., and Hatefi, Y., 1976, Oxidative phosphorylation properties of mito-chondria isolated from transplanted hepatoma, Biochim. Biophys. Acta 449:224–235.PubMedCrossRefGoogle Scholar
  155. Kawai, S., Yahata, N., Nishida, S., Nagai, K., and Mizushima, Y., 1995, Dehydroepiandrosterone inhibits B16 mouse melanoma cell growth by induction of differentiation, Anticancer Res. 15:427–431.PubMedGoogle Scholar
  156. Keller, G.-A., Barton, M. C., Shapiro, D. J., and Singer, S. J., 1985, 3-Hydroxy-3-methylglutaryl coenzyme A reductase is present in peroxisomes in normal rat liver cells, Proc. Natl. Acad. Sci. USA 82:770–774.PubMedCrossRefGoogle Scholar
  157. Keller, G.-A., Cable, S., El Bouhtoury, F., Heusser, S., Scotto, C., Armbruster, L., Ciolek, E., Colin, S., Schilt, J., and DauAa, M., 1993, Peroxisomes through cell differentiation and neoplasia, Biol. Cell 77:77–88.PubMedCrossRefGoogle Scholar
  158. Keyomarsi, K., Sandoval, L., Band, V., and Pardee, A. B., 1991, Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin, Cancer Res. 51:3602–3609.PubMedGoogle Scholar
  159. Keys, A., Aravanis, C., Blackburn, H., Buzina, R., Dontas, A. S., Fidanza, F., Karvonen, M. J., Menotti, A., Nedeljkovic, S., and Punsar, S., 1985, Serum cholesterol and cancer mortality in the Seven Countries study, Am. J. Epidemiol. 121:870–883.PubMedGoogle Scholar
  160. Khosravi-Far, R., Lutz, R. J., Cox, A. D., Conroy, L., Bournes, J. R., Sinensky, M., Balch, W. E., Buss, J. E., and Der, C. J., 1991, Isoprenoid modification of rab proteins terminating in CC or CXC motifs, Proc Natl Acad. Sci. USA 88:6264–6268.PubMedCrossRefGoogle Scholar
  161. Khosravi-Far, R., Clark, G. J., Abe, K., Cox, A. D., McLain, T., Lutz, R. J., Sinensky, M., and Der, C. J., 1992, Ras (CXXX) and Rab (CC/CXC) prenylation signal sequences are unique and functionally distinct, J. Biol. Chem. 267:24363–24368.PubMedGoogle Scholar
  162. Kinsella, B., and Maltese, W., 1992, rab GTP-binding proteins with three different carboxyl-terminal cysteine motifs are modified in vivo by 20-carbon isoprenoids, J. Biol. Chem. 267:3940–3945.PubMedGoogle Scholar
  163. Knekt, P., Reunanen, A., Aromaa, A., Heliovaara, M., Hakulinen, T., and Hakama, M., 1988, Serum cholesterol and risk of cancer in a cohort of 39,000 men and women, J. Clin. Epidemiol. 41:519–530.PubMedCrossRefGoogle Scholar
  164. Kohl, N., Diehl, R., Shaber, M., Rands, E., Soderman, D., He, B., Moores, S., Pompliano, D., Ferro-Novick, S., Powers, S., Thomas, K., and Gibbs, J. B., 1991, Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein transferases, J. Biol. Chem. 266: 18884–18888.PubMedGoogle Scholar
  165. Kohl, N. E., Mosser, S. D., deSolms, J., Guiliani, E. A., Pompliano, D. L., Graham, S. L., Smith, R. L., Scolnick, E. M., Oliff, A., and Gibbs, J. B., 1993, Selective inhibition of ras-dependent transformation by a farneslytransferase inhibitor, Science 260:1937–1943.CrossRefGoogle Scholar
  166. Kohl, N. E., Wilson, F. R., Mosser, S. D., Giuliani, E. A., deSolmes, S. J., Conner, M. W., Anthony, M. J., Holtz, W. J., Gomez, R. P., Lee, T.-J., Smith, R. L., Graham, S. L., Hart-man, G. D., Gibbs, J. B., and Oliff, A., 1994, Protein farnesyl transferase inhibitors block the growth of ras-dependent tumors in nude mice, Proc. Natl. Acad. Sci. USA 91: 9141–9145.PubMedCrossRefGoogle Scholar
  167. Kohl, N. E., Omer, C. A., Conner, M. W., Anthony, N. J., Davide, J. P., deSolms, S. J., Guiliani, W. A., Gomez, R. P., Graham, S. L., Hamilton, K., Handt, L. K., Hartman, G. D., Koblan, K. S., Kral, A. M., Miller, P. J., Mosser, S. D., O’Neill, T. J., Rands, E., Schaber, M. D., Gibbs, J. B., and Oliff, A., 1995, Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice, Nature Medicine 1:792–797.PubMedCrossRefGoogle Scholar
  168. Komiyama, K., Lizuka, K., Yamaoka, M., Watanabe, H., Tsuchiya, N., and Umezawa, I., 1989, Studies on the biological activity of tocotrienols, Chem. Pharm. Bull. 37:1369–1371.PubMedCrossRefGoogle Scholar
  169. Komori, A., Suganuma, M., Okabe, S., Zou, X., Tius, M. A., and Fujuki, H., 1993, Caventrol inhibits tumor promotion in CD-1 mouse skin through inhibition of tumor necrosis factor α release and protein isoprenylation, Cancer Res. 53:3462–3464.PubMedGoogle Scholar
  170. Kothapalli, R., Guthrie, N., Chambers, A. F., and Carroll, K. K., 1993, Farnesylamine: an inhibitor or farnesylation and growth of ras-transformed cells, Lipids 28:969–973.PubMedCrossRefGoogle Scholar
  171. Krämer, R., 1982, Cholesterol as activator of ADP-ATP exchange in reconstituted liposomes and in mitochondria, Biochim. Biophys. Acta 693:296–304.PubMedCrossRefGoogle Scholar
  172. Krisans, S. K., 1992, The role of peroxisomes in cholesterol metabolism, Am. J. Respir. Cell Mol. Biol. 7:358–364.PubMedGoogle Scholar
  173. Krisans, S. K., 1996, Cell compartmentalization of cholesterol biosynthesis, in: Peroxisomes: Biology and Role in Toxicology and Disease (J. K. Reddy, T. Suga, G. P. Mannaerts, S. Subramani, and P. B. Lazerow, eds.) Annals New York Acad. Sci. 804: 142–164.Google Scholar
  174. Krisans, S. K., Motensen, R. M., and Lazarow, P. B., 1980, Acyl CoA synthetase in rat liver peroxisomes: computer-assisted analysis of cell fractionation experiments, J. Biol. Chem. 255: 9599–9607.PubMedGoogle Scholar
  175. Krisans, S. K., Rusnak, N., Keller, G.-A., and Edwards, P. A., 1988, Localization of 3-hydroxy-3-methylglutaryl coenzyme A synthase in rat liver peroxisomes, J. Cell Biol. 107:122a.Google Scholar
  176. Krisans, S. K., Ericsson, J., Edwards, P. A., and Keller, G. A., 1994, Farnesyl-diphosphate synthase is localized in peroxisomes, J. Biol. Chem. 269:14165–14169.PubMedGoogle Scholar
  177. Kromhout, D., Bosschieter, E. B., Dreijver, M., and de Lezenne Coulander, C., 1988, Serum cholesterol and 25-year incidence of and mortality from myocardial infarction and cancer: the Zutphen study, Arch. Intern. Med. 148:1051–1055.PubMedCrossRefGoogle Scholar
  178. Kuroda, Y., Suzuki, N., and Kataoka, T., 1993, The effect of posttranslational modifications on the interaction of Ras2 with adenylyl cyclase, Science 259:683–686.PubMedCrossRefGoogle Scholar
  179. Langan, T. J., and Volpe, J. J., 1987, Cell cycle-specific requirement for mavalonate, but not for cholesterol, for DNA synthesis in glial primary cultures, J. Neurochem. 49:513–521.PubMedCrossRefGoogle Scholar
  180. Langan, T. J., and Volpe, J. J., 1987, Oligodendroglial differentiation in glial primary cultures: requirement for mevalonate, J. Neurochem. 48:1804–1808.PubMedCrossRefGoogle Scholar
  181. Lange, Y., 1992, Tracking cell cholesterol with cholesterol oxidase, J. Lipid Res. 33:315–321.PubMedGoogle Scholar
  182. Lange, Y., Swaisgood, M. H., Ramos, B. V., and Steck, T. L., 1989, Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts, J. Biol. Chem. 264:3786–3793.PubMedGoogle Scholar
  183. LaNoue, K. F., and Schoolwerth, A. C., 1979, Metabolite transport in mitochondria, Annu. Rev. Biochem. 48:871–922.PubMedCrossRefGoogle Scholar
  184. LaNoue, K. F., and Schoolwerth, A. C., 1984, Metabolite transport in mammmalian mitochondria, in: Bioenergetics (L. Ernster, ed.), pp. 221–268, Elsevier, NYGoogle Scholar
  185. Lardy, H., Partridge, B., and Wei, Y., 1995, Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone, Proc. Natl. Acad. Sci. USA 92: 6617–6619.PubMedCrossRefGoogle Scholar
  186. Lavietes, B., and Coleman, P. S., 1980, The role of lipid metabolism in neoplastic differentiation, J. Theor. Biol. 85:523–542.PubMedCrossRefGoogle Scholar
  187. Leevers, S. J., Paterson, H. F., and Marshall, C. J., 1994, Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane, Nature 369:411–414.PubMedCrossRefGoogle Scholar
  188. Leftheris, K., Kline, T., Vite, G. D., Cho, Y H., Bhide, R. S., Patel, D. V., Patel, M. M., Schmidt, R. J., Weller, H. N., Andahazy, M. L., Carboni, J. M., Gullo-Brown, J. L., Lee, F. Y., Ricca, C., Rose, W. C., Yan, N., Barbacid, M., Hunt, J. T., Meyers, C. A., Seizinger, B. R., Zahler, R., and Manne, V., 1996, Development of highly potent inhibitors of Ras farensyltransferase possessing cellular and in vivo activity, J. Med. Chem. 39: 224–236.PubMedCrossRefGoogle Scholar
  189. Leonard, S., Beck, L., and Sinensky, M., 1990, Inhibition of isoprenoid biosynthesis and the post-translatinal modification of pro-p21ras, J. Biol. Chem. 265:5157–5160.PubMedGoogle Scholar
  190. Lerner, E. C., Qian, Y., Hamilton, A. D., and Sebti, S. M., 1996, Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor J. Biol. Chem. 270: 26770–26773.Google Scholar
  191. Lin, D., Sugawara, T., Strauss III, J. F., Clark, B. J., Stocco, D. M., Saenger, P., Rogol, A., and Miller, W. L., 1995, Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis, Science 267:1828–1831.PubMedCrossRefGoogle Scholar
  192. Liscum, L., and Dahl, N. K., 1992, Intracellular cholesterol transport, J. Lipid Res. 33:1239–1254.PubMedGoogle Scholar
  193. Liscum, L., and Underwood, K. W., 1995, Intracellular cholesterol transport and compartmentation, J. Biol. Chem. 270:15443–15446.PubMedCrossRefGoogle Scholar
  194. Liu, W. C., Barbacid, M., Bulgar, M., Clark, J. M., Crosswell, A. R., Dean, L., Doyle, T. W., Fernandes, P. B., Huang, S., Manne, V., Pirnik, D. M., Wells, J. S., and Meyers, E., 1992, 10′-desmethoxystreptonigrin, a novel analog of streptonigrin, J. Antibiot. 45:454–457.PubMedCrossRefGoogle Scholar
  195. Liu, L., Shack, S., Stetler-Stevenson, W., Hudgins, W. R., and Samid, D., 1994, Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenyl-butyrate, J. Invest. Dermatol 103:335–340.PubMedCrossRefGoogle Scholar
  196. Liu, L., Hudgins, W. R., Shack, S., Yin, M. Q., and Samid, D., 1995, Cinnamic acid: a natural product with potential use in cancer intervention, Int. J. Cancer 62:345–350.PubMedCrossRefGoogle Scholar
  197. Maltese, W. A., 1990, Posttranslational modification of proteins by isoprenoids in mammalian cells, FASEB J. 4:3319–3328.PubMedGoogle Scholar
  198. Maltese, W. A., and Aprille, J. R., 1985, Relation of mevalonate synthesis to mitochondrial ubiquinone content and respiratory function in cultured neuroblastoma cells, J. Biol. Chem. 260: 11524–11529.PubMedGoogle Scholar
  199. Maltese, W. A., and Sheridan, K. M., 1987, Isoprenylated proteins in cultured cells: subcellular distribution and changes related to altered morphology and growth arrest induced by mevalonate deprivation, J. Cell Physiol 133:471–481.PubMedCrossRefGoogle Scholar
  200. Maltese, W. A., and Sheridan, K. M., 1988, Isoprenoid synthesis during the cell cycle, J. Biol. Chem. 263:10104–10110.PubMedGoogle Scholar
  201. Maltese, W. A., and Sheridan, K. M., 1988, Studies of 3-hydroxy-3-methylglutaryl coenzyme A synth-ease and reductase and isoprenoid labeling in cells synchronized by centrifugal elutriation, J. Biol Chem. 263:10104–10110.PubMedGoogle Scholar
  202. Maltese, W. A., Defendi, R., Green, R. A., Sheridan, K. M., and Donley, D. K., 1985, Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, J. Clin. Invest. 76:1748–1754.PubMedCrossRefGoogle Scholar
  203. Manne, V., Yan, N., Carboni, J. M., Tuomari, A. V., Ricca, C. S., Brown, J. G., Andahazy, M. L., Schmidt, R. J., Patel, D., Zahler, R., Weinmann, R., Der, C. J., Cox, A. D., Hunt, J. T., Gordon, E. M., Barbacid, M., and Seizinger, B. R., 1995, Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells, Oncogenes 10:1763–1779.Google Scholar
  204. Marom, M., Haklai, R., Ben-Baruch, G., Marciano, D., Egozi, Y., and Kloog, Y., 1995, Selective inhibition of Ras-dependent cell growth by farnesylthiosalicylic acid, J. Biol. Chem. 270: 22263–22270.PubMedCrossRefGoogle Scholar
  205. Marshall, C. J., 1993, Protein prenylation: a mediator of protein-protein interactions, Science 259:1865–1866.PubMedCrossRefGoogle Scholar
  206. Marshall, C. J., 1995, Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation, Cell 80:179–185.PubMedCrossRefGoogle Scholar
  207. Marshall, M. S., 1993, The effector interactions of p21ras, Trends Biochem. Sci. 18:250–254.PubMedCrossRefGoogle Scholar
  208. Marsters, J. C. J., McDowell, R. S., Reynolds, M. E., Oare, D. A., Somers, T. C., Stanley, M. S., Raw-son, T. E., Struble, M. E., Burdick, D. J., and Chan, K. S., 1994, Benzodiazepine peptidomimetic inhibition of farnesyltransferase, Bioorg. Med. Chem. 2:949–957.PubMedCrossRefGoogle Scholar
  209. Martinez, F., Eschegoyen, S., Briones, R., and Cuellar, A., 1988, Cholesterol increase in mitochondria: a new method of cholesterol incorporation, J. Lipid Res. 29:1005–1011.PubMedGoogle Scholar
  210. Maxwell, R. E., Nawrocki, J. W., and Uhlendorf, P. D., 1983, Some comparative effects of gemfibrozil, Clofibrate, bezafibrate, cholestyramine and compactin on sterol metabolism in rats, Atherosclerosis 48:195–203.PubMedCrossRefGoogle Scholar
  211. McGeady, P., Kuroda, S., Shimizu, K., Takai, Y., and Gelb, M. H., 1995, The farnesyl group of H-Ras facilitates the activation of a soluble upstream activator of mitogen-activated protein kinase, J. Biol. Chem. 270:26347–26351.PubMedCrossRefGoogle Scholar
  212. Medema, R. H., and Bos, J. L., 1993, The role of p21ras in receptor tyrosine kinase signaling, Crit. Rev. Oncogenesis 4:15–61.Google Scholar
  213. Meigs, T. E., Sherwood, S. W., and Simoni, R. D., 1995, Farnesyl acetate, a derivative of an isoprenoid of the mevalonate pathway, inhibits DNA replication in hamster and human cells, Exp. Cell Res. 219:461–470.PubMedCrossRefGoogle Scholar
  214. Middleton, A., Middleton, B., White, D. A., and Bell, G. D., 1979, The effects of monocyclic ter-penes on hepatic S-3-hydroxy-3-methylglutaryl coenzyme A reductase in vivo, Biochem. Soc. Trans. 7:407–408.PubMedGoogle Scholar
  215. Miller, A. C., and Samid, D., 1994, Tumor resistance to oxidative stress: association with ras oncogene expression and reversal by lovastatin, an inhibitor of P21 ras isoprenylation, Int. J. Cancer 59:1–6.CrossRefGoogle Scholar
  216. Miller, A. C., Kariko, K., Myers, C. E., Clark, E. P., and Samid, D., 1993, Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21 ras isoprenylation, Int. J. Cancer 53:302–307.PubMedCrossRefGoogle Scholar
  217. Miura, S., Hasumi, K., and Endo, A., 1993, Inhibition of protein prenylation by patulin, FEBS Lett. 318:88–90.PubMedCrossRefGoogle Scholar
  218. Montgomery, R. B., Moscatello, D. K., Wong, A. J., Cooper, J. A., and Stahl, W. L., 1995, Differential modulation of mitogen-activated protein (MAP) kinase/extracellular signal-related kinase kinase and MAP kinase activities by a mutant epidermal growth factor receptor, J. Biol. Chem. 270: 30562–30566.PubMedCrossRefGoogle Scholar
  219. Moomaw, J., and Casey, P., 1992, Mammalian protein geranylgeranyltransferase, J. Biol. Chem. 267: 17438–17443.PubMedGoogle Scholar
  220. Moores, S. L., Schaber, M., Mosser, S., Rands, E., O’Hara, M., Garsky, V., Marshall, M., Pompli-ano, D., and Gibbs, J., 1991, Sequence dependence of protein isoprenylation, J. Biol. Chem. 266:14603–14610.PubMedGoogle Scholar
  221. Moreadith, R. W., and Lehninger, A. L., 1984, The pathways of glutamate and glutamine oxidation by tumor cell mitochondria, J. Biol. Chem. 259:6215–6221.PubMedGoogle Scholar
  222. Mortensen, P. B., Kristensen, S. D., Bloch, A., Jacobsen, B. A., and Rasmussen, S. N., 1988, Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy, Scand. J. Gastroenterol. 23:1085–1088.PubMedCrossRefGoogle Scholar
  223. Morton, R., Cunningham, C., Jester, R., Waite, M., Miller, N., and Morris, H. P., 1976, Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma, Cancer Res. 36: 3246–3254.PubMedGoogle Scholar
  224. Nagasu, T., Yoshimatsu, K., Rowell, C., Lewis, M. D., and Garcia, A. M., 1995, Inhibition of human tumor xenograft growth by treatment with farnesyl transferase inhibitor B956, Cancer Res. 55:5310–5314.PubMedGoogle Scholar
  225. Nave, J.-E, d’Orchymont, H., Ducep, J.-B., Piriou, F., and Jung, M., 1985, Mechanism of the inhibition of cholesterol biosynthesis by 6-fluoromevalonate, Biochem. J. 227:247–254PubMedGoogle Scholar
  226. Nestler, J. E., Takagi, K., and Strauss III, J. F., 1990, Lipoprotein and cholesterol metabolism in cells that synthesize steroid hormones, in: Advances in Cholesterol Research (M. Esfahani and J. Swaney, eds.), pp. 133–169, Telford Press, Caldwell, NJ.Google Scholar
  227. Newman, C. M. H., and Magee, A. I., 1993, Posttranslational processing of the ras superfamily of small GTP-binding proteins, Biochim. Biophys. Acta 1155:79–96.PubMedGoogle Scholar
  228. Nigam, M., Seong, C.-M., Qian, Y., Hamiton, A. D., and Sebti, S. M., 1993, Potent inhibition of human tumor p21ras farnesyltransferase by A1A2-lacking p21ras CA1 A2X peptidomimetics, J. Biol. Chem. 269:20695–20698.Google Scholar
  229. Nigg, E. A., Kitten, G. T., and Vorburger, K., 1992, Targeting lamin proteins to the nuclear envelope: the role of CaaX box modifications, Biochem. Soc. Trans. 20:500–504.PubMedGoogle Scholar
  230. Norbury, C., and Nurse, P., 1992, Animal cell cycles and their control., Annu. Rev. Biochem. 61: 441–470.PubMedCrossRefGoogle Scholar
  231. Okwu, A. K., Xu, X.-X., Shiratori, Y., and Tabas, I., 1994, Regulation of the threshold for lipoprotein-induced acyl-CoAxholesterol O-acyltransferase stimulation in macrophages by cellular sphingomyelin content, J. Lipid Res. 35:644–655.PubMedGoogle Scholar
  232. Omer, C.A., Kral, A.M., Diehl, R.E., Prendergast, G.C., Powers, S., Allen, CM., Gibbs, J.B., and Kohl, N.E., 1993, Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding and functional homology with yeast prenyl-protein transferases, Biochemistry 32:5167–5176.PubMedCrossRefGoogle Scholar
  233. Omura, S., van der Pyl, D., Inokoshi, J., and Takashima, H., 1993, Pepticinnamins, new farnesyl-protein tranferase inhibitors produced by an actinomycete. I. Producing strain, fermentation, isolation and biological activity, J. Antibiot. 46:222–228.PubMedCrossRefGoogle Scholar
  234. Op den Kamp, J. A. F., 1979, Lipid asymmetry in membranes, Annu. Rev. Biochem. 48:47–71.CrossRefGoogle Scholar
  235. Pani, P., Canuto, R., Garcea, R., and Feo, F., 1973, Lipid composition of subcellular particles isolated from rat liver and tumor cells, Biochem. Soc. Trans. 1:972–976.Google Scholar
  236. Pardee, A. B., 1989, G1 events and regulation of cell proliferation, Science 246:603–608.PubMedCrossRefGoogle Scholar
  237. Parker, R. A., Pearce, B. C., Clark, R. W., Gordon, D. A., and Wright, J. J. K., 1993, Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, J. Biol. Chem. 268:11230–11238.PubMedGoogle Scholar
  238. Parlo, R. A., and Coleman, P. S., 1984, Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria, J. Biol. Chem. 259:9997–10003.PubMedGoogle Scholar
  239. Parlo, R. A., and Coleman, P. S., 1986, Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas, Biochim. Biophys. Acta 886: 169–176.PubMedCrossRefGoogle Scholar
  240. Patel, D. V., Gordon, E. M., Schmidt, R. J., Weller, H. N., Young, M. G., Zahler, R., Barbacid, M., Carboni, J. M., Gullo-Brown, J. L., Hunihan, L., Ricca, C., Robinson, S., Seizinger, B. R., Tuomari, A. V., and Manne, V., 1995, Phosphinyl acid-based bisubstrate analog inhibitors of Ras farnesyl protein transferase, J. Med. Chem. 38:435–442.PubMedCrossRefGoogle Scholar
  241. Pearce, B. C., Parker, R. A., Deason, M. E., Qureshi, A. A., and Wright, J. J. K., 1992, Hypocholes-terolemic activity of synthetic and natural tocotrienols, J. Med. Chem. 35:3595–3606.PubMedCrossRefGoogle Scholar
  242. Pearce, B. C., Parker, R. A., Deason, M. E., Dischino, D. D., Gillespie, E., Qureshi, A. A., Volk, K., and Wright, J. J. K., 1994, Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols, J. Med. Chem. 37:526–541.PubMedCrossRefGoogle Scholar
  243. Pedersen, P. L., 1978, Tumor mitochondria and the bioenergetics of cancer cells, in: Prog. Exp. Tumor Res. (D. F. H. Wallach, ed.), pp. 190–274, S. Karger, Basel.Google Scholar
  244. Peeper, D. S., van der Eb, A. J., and Zantema, A., 1994, The G1/S cell-cycle checkpoint in eukaryotic cells, Biochim. Biophys. Acta 1198:215–230.PubMedGoogle Scholar
  245. Perez-Sala, D., and Mollinedo, F., 1994, Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL-60 cells, Biochem. Biophys. Res. Commun. 199:1209–1215.PubMedCrossRefGoogle Scholar
  246. Perkins, S. L., Ledin, S. F., and Stubbs, J. D., 1982, Linkage of the isoprenoid biosynthetic pathway with induction of DNA synthesis in mouse lymphocytes. Effects of compactin on mitogen-induced lymphocytes in serum-free medium, Biochim. Biophys. Acta 711:83–89.PubMedCrossRefGoogle Scholar
  247. Pompliano, D., Rands, E., Schaber, M., Mosser, S., Anthony, N., and Gibbs, J., 1992, Steady-state kinetic mechanism of Ras farnesyl:protein transferase, Biochemistry 31:3800–3807.PubMedCrossRefGoogle Scholar
  248. Powers, S., Michaelis, S., Broek, D., S., A.-A., Field, J., Herskowitz, I., and Wigler, M., 1986, RAM, a gene of yeast required for a functional modification of RAS proteins and for production of mating pheromone a-factor, Cell 47:413–422.PubMedCrossRefGoogle Scholar
  249. Prager, C., Schön, H. J., Nikfardjam, M., Schmid, D., Untersalmberger, M., Kremser, K., and Kramar, R., 1993, Clofibrate elevates enzyme activities of the tricarboxylic acid cycle in rat liver, J. Lipid Res. 34:359–364.PubMedGoogle Scholar
  250. Prendergast, G.C., and Gibbs, J. B., 1994, Ras regulatory interactions: Novel targets for anti-cancer intervention?, BioEssays 16:187–191.PubMedCrossRefGoogle Scholar
  251. Prendergast, G. C., Davide, J. P., deSolms, S. J., Giuliani, E. A., Graham, S. L., Gibbs, J. B., Oliff, A., and Kohl, N. E., 1994, Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechansim that involves regulation of the actin cytoskeleton, Mol Cell Biol. 14:4193–4202.PubMedGoogle Scholar
  252. Privalle, C. T., Crivello, J. F., and Jefcoate, C. R., 1983, Regulation of intramitochondrial cholesterol transfer to side-chain cleavage cytochrome P-450 in rat adrenal gland, Proc. Natl. Acad. Sci. USA 80:702–706.PubMedCrossRefGoogle Scholar
  253. Qian, Y., Blaskovich, M. A., Saleem, M., Seong, C.-M., Wathen, S. P., Hamilton, A. D., and Sebti, S. M., 1994, Design and structural requirements of potent peptidomimetic inhibitors of p21ras farnesyltransferase, J. Biol. Chem. 269:12410–12413.PubMedGoogle Scholar
  254. Quesney-Huneeus, V., Wiley, M. H., and Siperstein, M. D., 1979, Essential role for mevalonate synthesis in DNA replication, Proc. Natl Acad. Sci. USA 76:5056–5060.PubMedCrossRefGoogle Scholar
  255. Quesney-Huneeus, V., Galick, H. A., Siperstein, M. D., Erickson, S. K., Spencer, T. A., and Nelson, J. A., 1983, The dual role of mevalonate in the cell cycle, J. Biol. Chem. 258:378–385.PubMedGoogle Scholar
  256. Quilliam, L. A., Huff, S. Y., Rabun, K. M., Wei, W., Park, W., Broek, D., and Der, C. J., 1994, Membrane-targeting potentiates guanine nucleotide exchange factor CDC25 and SOS1 activation of Ras transforming activity, Proc. Natl. Acad. Sci. USA 91:8512–8516.PubMedCrossRefGoogle Scholar
  257. Qureshi, A. A., Mangels, A. R., Din, Z. Z., and Elson, C. E., 1988, Inhibition of hepatic mevalonate biosynthesis by the monoterpene, D-limonene., J. Agric. Food Chem. 36:1220–1224.CrossRefGoogle Scholar
  258. Ram, Z., Samid, D., Walbridge, S., Oshiro, E. M., Viola, J. J., Tao-Cheng, J.-H., Shack, S., Thibault, A., Meyers, C. E., and Oldfield, E. H., 1994, Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate, Cancer Res. 54: 2923–2927.PubMedGoogle Scholar
  259. Rao, K. N., 1995, The significance of the cholesterol biosynthetic pathway in cell growth and carcinogenesis, Anticancer Res. 15:309–314.PubMedGoogle Scholar
  260. Rao, S., and Coleman, P. S., 1989, Control of DNA replication and cell growth by inhibiting the export of mitochondrially derived citrate, Exp. Cell Res. 180:341–352.PubMedCrossRefGoogle Scholar
  261. Reardon, J. E., and Abeles, R. H., 1987, Inhibition of cholesterol biosynthesis by fluorinated mevalonate analogues, Biochemistry 26:4717–4722.PubMedCrossRefGoogle Scholar
  262. Reddy, J. K., and Lalwani, N. D., 1983, Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans, Crit. Res. Toxicol 12:1–58.CrossRefGoogle Scholar
  263. Reddy, J. K., and Mannaerts, G. P., 1994, Peroxisomal lipid metabolism, Annu. Rev. Nutr. 14:343–370.PubMedCrossRefGoogle Scholar
  264. Regelson, W., and Kalimi, M., 1994, Dehydroepiandrosterone (DHEA)—the multifunctional steroid. II. Effects on the CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of action? Ann. NY Acad. Sci. 719:564–575.PubMedCrossRefGoogle Scholar
  265. Reiss, Y., Goldstein, J. L., Seabra, M. C., Casey, P. J., and Brown, M. S., 1990, Inhibition of purified p21ras farnesyliprotein transferase by Cys-AAX tetrapeptides, Cell 62:81–88.PubMedCrossRefGoogle Scholar
  266. Reiss, Y., Seabra, M., Armstrong, S., Slaughter, C., Goldstein, J., and Brown, M., 1991, Non-identical subunits of p21ras farnesyltransferase: peptide binding and farnesyl pyrophosphate carrier functions, J. Biol. Chem. 266:10672–10677.PubMedGoogle Scholar
  267. Reiss, Y., Stradley, S., Gierasch, L. M., Brown, M. S., and Goldstein, J. L., 1991, Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase, Proc. Natl. Acad. Sci. USA 88:732–736.PubMedCrossRefGoogle Scholar
  268. Reiss, Y., Brown, M. S., and Goldstein, J. L., 1992, Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme, J. Biol. Chem. 267:6404–6408.Google Scholar
  269. Ridley, A. J., and Hall, A., 1992, The small GTP binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors, Cell 70:389–399.PubMedCrossRefGoogle Scholar
  270. Rilling, H. C., Bruenger, E., Epstein, W. W., and Crain, P. F., 1990, Prenylated proteins: the structure of the isoprenoid group, Science 247:318–320.PubMedCrossRefGoogle Scholar
  271. Rosen, N., 1995, Oncogenes, in: The Molecular Basis of Cancer (J. Mendelsohn, P. M. Howley, M. A. Israel, and L. A. Liotta, eds.), pp. 105–116, W. B. Saunders Company, Philadelphia.Google Scholar
  272. Rothblat, G. H., Mahlberg, F.H., Johnson, W. J., and Phillips, M. C., 1992, Apolipoproteins, membrane cholesterol domains and the regulation of cholesterol efflux, J. Lipid Res. 33: 1091–1097.PubMedGoogle Scholar
  273. Roussillon, S., Astruc, M., Defay, R., Tabacik, C., Descomps, B., and Crastes de Paulet, A., 1983, DNA and cholesterol biosynthesis in synchronized embryonic rat fibroblasts. Temporal relationships between HMG-CoA reductase activity, sterol biosynthesis and thymidine incorporation into DNA, Biochim. Biophys. Acta 763:1–10.PubMedCrossRefGoogle Scholar
  274. Ruch, R. J., and Sigler, K., 1994, Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not involve Ras plasma membrane association, Carcinogenesis 15:787–789.PubMedCrossRefGoogle Scholar
  275. Ruderman, J. V., 1993, MAP kinase and the activation of quiescent cells, Curr. Opin. Cell Biol. 5: 207–213.PubMedCrossRefGoogle Scholar
  276. Rudney, H., and Sexton, R. C., 1986, Regulation of cholesterol biosynthesis, Annu. Rev. Nutr. 6: 245–272.PubMedCrossRefGoogle Scholar
  277. Rusnak, N., and Krisans, S. K., 1987, Diurnal variation of HMG-CoA reductase activity in rat liver peroxisomes, Biochem. Biophys. Res. Commun. 148:890–896.PubMedCrossRefGoogle Scholar
  278. Sabine, J. R., 1975, Defective control of lipid biosynthesis in cancerous and precancerous liver, Prog. Biochem. Pharmacol. 10:269–307.PubMedGoogle Scholar
  279. Samid, D., Miller, A. C., Rimoldi, D., Gafner, J., and Clark, E. P., 1991, Increased radiation resistance in transformed and non-transformed cells with elevated ras proto-oncogene expression, Rad. Res. 126:244–250.CrossRefGoogle Scholar
  280. Samid, D., Shack, S., and Sherman, L. T., 1992a, Phenylacetate: a novel nontoxic inducer of tumor cell differentiation, Cancer Res. 52:1988–1992.PubMedGoogle Scholar
  281. Samid, D., Yeh, A., and Prasanna, P., 1992b, Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate, Blood 80: 1576–1581.PubMedGoogle Scholar
  282. Samid, D., Shack, S., and Meyers, C. E., 1993, Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate, J. Clin. Invest. 91:2288–2295.PubMedCrossRefGoogle Scholar
  283. Samid, D., Ram, Z., Hudgins, W. R., Shack, S., Liu, L., Walbridge, S., Oldfield, E. H., and Myers, C. E., 1994, Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria, Cancer Res. 54:891–895.PubMedGoogle Scholar
  284. Sanford, J. C., Foster, L., Kapadia, Z., and Wessling-Resnick, M., 1995, Analysis of the stoichiometry of Rab protein prenylation, Anal. Biochem. 224:547–556.PubMedCrossRefGoogle Scholar
  285. Sapperstein, S., Berkower, C., and Michaelis, S., 1994, Nucleotide sequence of the yeast STE14 gene which encodes an isoprenylcysteine carboxyl methyltransferase and demonstration of its essential role in a-factor export, Mol. Cell Biol. 14:1438–1449.PubMedGoogle Scholar
  286. Sawamura, M., Li, N., Nara, Y., and Yamori, Y., 1993, Proliferative effect of mevalonate metabolites other than isoprenoids on cultured vascular smooth muscle cells, Clin. Exp. Pharm. Physiol. 20: 509–514.CrossRefGoogle Scholar
  287. Schafer, W. R., and Rine, J., 1992, Protein prenylation: genes enzymes, targets and functions, Annu. Rev. Genet. 26:209–237.PubMedCrossRefGoogle Scholar
  288. Schatzkin, A., Hoover, R. N., Taylor, P. R., Zeigler, R. G., Carter, C. L., Albanes, D., Larson, D. B., and Licitra, L. M., 1988, Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study, Cancer Res. 48:452–458.PubMedGoogle Scholar
  289. Schepers, L., Casteels, M., Vamecq, J., Parmentier, G., van Veldhoven, P. P., and Mannaerts, G. P., 1988, β-Oxidation of the carboxyl side-chain of prostaglandin E2 in rat liver peroxisomes and mitochondria, J. Biol. Chem. 263:2724–2731.PubMedGoogle Scholar
  290. Schepers, L., van Veldhoven, P. P., Casteels, M., Eyssen, H., and Mannaerts, G. P., 1990, Presence of three acyl-CoA oxidases in rat liver peroxisomes, J. Biol. Chem. 265:5242–5246.PubMedGoogle Scholar
  291. Schmidt, R. A., Schneider, C. L., and Glomset, J. A., 1984, Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins, J. Biol. Chem. 259:10175–10180.PubMedGoogle Scholar
  292. Schneider, H., Lemasters, J. J., Höchli, M., and Hackenbrock, C. R., 1980, Fusion of liposomes with mitochondrial inner membranes, Proc. Natl. Acad. Sci. USA 77:442–446.PubMedCrossRefGoogle Scholar
  293. Schneider, H., Lemasters, J. J., Höchli, M., and Hackenbrock, C. R., 1980, Liposome-mitochondrial inner membrane fusion, J. Biol. Chem. 255:3748–3756.PubMedGoogle Scholar
  294. Schneider, H., Höchli, M., and Hackenbrock, C. R., 1982, Relationship between the density distribution of intramembrane particles and electron transfer in the mitochondrial inner membrane as revealed by cholesterol incorporation, J. Cell Biol. 94:387–393.PubMedCrossRefGoogle Scholar
  295. Schultz, S., and Nyce, J. W., 1991, Inhibition of protein isoprenylation and p21ras membrane association by dehydroepiandrosterone in human colonic adenocarcinoma cells in vitro, Cancer Res. 51:6563–6567.Google Scholar
  296. Schultz, S., Klann, R. C., Schonfeld, S., and Nyce, J. W., 1992, Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis, Cancer Res. 52:1372–1376.Google Scholar
  297. Schwartz, A. G., Whitcomb, J. M., Nyce, J. W., Lewbart, M. L., and Pashko, L. L., 1988, Dehydroepiandrosterone and structural analogs: a new class of cancer chemopreventive agents, Adv. Cancer Res. 51:391–424.PubMedCrossRefGoogle Scholar
  298. Seabra, M., Goldstein, J., Sudhof, M., and Brown, M., 1992, Rab geranylgeranyl transferase, J. Biol. Chem. 267:14497–14503.PubMedGoogle Scholar
  299. Sebti, S. M., Tkalavic, G. T., and Jani, J. P., 1991, Lovastatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice, Cancer Commun. 3:141–147.PubMedGoogle Scholar
  300. Seedorf, U., Brysch, P., Engel, T., Schrage, K., and Assmann, G., 1994, Sterol carrier protein X is peroxisomal 3-oxoacyl CoA thiolase with intrinsic sterol carrier and lipid transfer activity, J. Biol. Chem. 269:21277–21283.PubMedGoogle Scholar
  301. Sepp-Lorenzino, L., Azrolan, N. I., and Coleman, P. S., 1989, Cellular distribution of cholesterogenesis-linked, phospho-isoprenylated proteins in proliferating cells, FEBS Lett. 245:110–116.PubMedCrossRefGoogle Scholar
  302. Sepp-Lorenzino, L., Rao, S., and Coleman, P. S., 1991, Cell-cycle-dependent, differential prenylation of proteins, Eur. J. Biochem. 200:579–590.PubMedCrossRefGoogle Scholar
  303. Sepp-Lorenzino, L., Coleman, P. S., and Larocca, J., 1994, Isoprenylated proteins in myelin, J. Neu-rochem. 62:1539–1545.Google Scholar
  304. Sepp-Lorenzino, L., Ma, Z., Kohl, N. E., Rands, E., Gibbs, J. B., Oliff, A., and Rosen, N., 1995, A peptidomimetic inhibitor of farnesyl:protein transferase inhibits the anchorage-dependent and-independent growth of human tumor cell lines, Cancer Res. 55:5302–5309.PubMedGoogle Scholar
  305. Shack, S., Chen, L.-C., Miller, A. C., Danesi, R., and Samid, D., 1995, Increased susceptibility of ras-transformed cells to phenylacetate is associated with inhibition of p21ras isoprenylation and phenotypic reversion, Intl. J. Cancer 63:124–129.CrossRefGoogle Scholar
  306. Shama Bhat, C., and Ramasarma, T., 1979a, Effect of phenyl and phenolic acids on mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase of the rat brain, J. Neurochem. 32:1531–1537.CrossRefGoogle Scholar
  307. Shama Bhat, C., and Ramasarma, T., 1979b, Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds, Biochem. J. 181:143–151.PubMedGoogle Scholar
  308. Sherwin, R. W., Wentworth, D. N., Cutler, J. A., Hulley, S. B., Kuller, L. H., and Stamler, J., 1987, Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial, JAMA 257:943–948.PubMedCrossRefGoogle Scholar
  309. Shiomi, K., Yang, H., Inokoshi, J., van der Pyl, D., Nakagawa, A., Takeshima, H., and Omura, S., 1993, Pepticinnamins, new farnesyl-protein tranferase inhibitors produced by an actinomycete. II. Structural elucidation of pepticinnamin E, J. Antibiot. 46:229–234.PubMedCrossRefGoogle Scholar
  310. Shirataki, H., Kaibuchi, K., Yamaguchi, T., Wada, K., Horiuchi, H., and Takai, Y., 1992, A possible target protein for smg-25A/rab3A small GTP-binding protein, J. Biol. Chem. 267: 10946–10949.PubMedGoogle Scholar
  311. Shu, Y. Z., Huang, S., Wang, R. R., Lam, K. S., Klohr, S. E., Volk, K. J., Pirnik, D. M., Wells, J. S., Fernandes, P. B., and Patel, P. S., 1994, Manumycins E, F, and G, new members of manumycin class antibiotics, from Streptomyces sp., J. Antibiot. 47:324–3PubMedCrossRefGoogle Scholar
  312. Singh, S. B., Zink, D. L., Liesch, J. M., Goetz, M. A., Jenkins, R. G., Nallin-Olmstead, M., Silverman, K. C., Bills, G. F., Mosley, R. T., Gibbs, J. B., Albers-Schonberg, G., and Lingham, R. B., 1993, Isolation and structure of chaetomellic acids A and B from Chaetomella acutiseta: farnesyl pyrophosphate mimic inhibitos or Ras farnesyl-protein transferase, Tetrahedron 49:5917–5926.CrossRefGoogle Scholar
  313. Siperstein, M. D., 1970, Regulation of cholesterol biosynthesis in normal and malignant tissues, in: Current Topics in Cell Regulation (B. L. Horecker and E. R. Stadtman, eds.), pp-65–100, Academic Press, New York.Google Scholar
  314. Siperstein, M. D., 1984, Role of cholesterogenesis and isoprenoid synthesis in DNA replication and cell growth, J. Lipid Res. 25:1462–1468.PubMedGoogle Scholar
  315. Siperstein, M. D., 1995, Cholesterol, cholesterogenesis and cancer, Adv. Exper. Med. Biol. 369: 155–166.CrossRefGoogle Scholar
  316. Skalnik, D. G., Brown, D. A., Borwn, P. C., Friedman, R. L., Hardeman, E. C., Schimke, R. T., and Simoni, R. D., 1985, Mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase over-accumulation in three compactin-resistant cell lines, J. Biol. Chem. 260:1991–1994.PubMedGoogle Scholar
  317. Slotte, J. P., Hedström, G., Rannström, S., and Ekman, S., 1989, Effects of sphingomyelin degradation on cell cholesterol oxidizability and steady-state distribution between the cell surface and the cell interior, Biochim. Biophys. Acta 985:90–96.PubMedCrossRefGoogle Scholar
  318. Smith, M. R., De Gudicibus, S. J., and Stacey, D. W., 1986, Requirement for c-ras proteins during viral oncogene transformation, Nature 320:540–543.PubMedCrossRefGoogle Scholar
  319. Soldati, T., Shaprio, A. D., Svejstrup, A. B. D., and Pfeffer, S. R., 1994, Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange, Nature 369:76–78.PubMedCrossRefGoogle Scholar
  320. Spady, D. K., 1991, Regulation of cholesterol metabolism in normal and malignantly transformed tissue in vivo, in: Chemical Carcinogenesis-2: Modulating Factors (A. Columbano, F. Feo, R. Pascale, and P. Pani, eds.), pp. 299–309, Plenum Press, NY.Google Scholar
  321. Spector, A. A., and Yorek, M. A., 1985, Membrane lipid composition and cellular function, J. Lipid Res. 26:1015–1035.PubMedGoogle Scholar
  322. Srere, P., 1975, The enzymology of the formation and breakdown of citrate, Adv. Enzymol. 43:57–101.PubMedGoogle Scholar
  323. Stamellos, K. D., Shackelford, J. E., Tanaka, R. D., and Krisans, S. K., 1992, Mevalonate kinase is localized in rat liver peroxisomes, J. Biol. Chem. 267:5560–5568.PubMedGoogle Scholar
  324. Stamellos, K. D., Shackelford, J. E., Shechter, I., Jiang, G., Conrad, D., Keller, G. A., and Krisans, S. K., 1993, Subcellular localization of squalene synthase in rat hepatic cells. Biochemical and immunochemical evidence, J. Biol. Chem. 268:12825–12836.PubMedGoogle Scholar
  325. Stange, E. F., Preclik, G., Schneider, A., and Reimann, F., 1988, The role of enterocyte cholesterol metabolism in intestinal cell growth and differentiation, Scand. J. Gastroent. 151:79–85.CrossRefGoogle Scholar
  326. Stimmel, J. B., Deschenes, R., Volker, C., Stock, J., and Clarke, S., 1990, Evidence for an S-farnesyl-cysteine methyl ester at the carboxyl terminus of the Saccharomyces cerevisiae RAS2 protein, Biochemistry 29:9651–9659.PubMedCrossRefGoogle Scholar
  327. Stokoe, D., Macdonald, S. G., Cadwallader, K., Symons, M., and Hancock, J. F., 1994, Activation of Raf as a result of recruitment to the plasma membrane, Science 264:1463–1467.PubMedCrossRefGoogle Scholar
  328. Stradley, S. J., Rizo, J., and Gierasch, L. M., 1993, Conformation of a heptapeptide substrate bound to protein farnesyltransferase, Biochemistry 32:12586–12590.PubMedCrossRefGoogle Scholar
  329. Sumi, S., Beauchamp, D., Townsend, C. M., Jr., Uchida, T., Murakami, M., Rajaraman, S., Ishizuka, J., and Thompson, J. C., 1992, Inhibition of pancreatic adenocarcinoma cell growth by lovastatin, Gastroenterology 103:982–989.PubMedGoogle Scholar
  330. Tabacik, C., and Aliau, S., 1989, Cholesterogenesis and cell division in phytohemagglutinin-stimulated human lymphocytes: a comparative study with several inhibitors, Biochim. Biophys. Acta 1011: 149–157.PubMedCrossRefGoogle Scholar
  331. Tamanoi, F., 1993, Inhibitors of Ras farnesyltransferases, Trends Biochem. Sci. 18:349–353.PubMedCrossRefGoogle Scholar
  332. Tertov, V. V., Orekhov, A. N., Ryong, L. H., and Smirnov, V. N., 1988, Intracellular cholesterol accumulation is accompanied by enhanced proliferative activity of human aortic intimal cells, Tissue Cell. 20:849–854.PubMedCrossRefGoogle Scholar
  333. Thibault, A., Cooper, M. R., Figg, W. D., Venzon, D. J., Sartor, A. O., Tompkins, A. C., Weinberger, M. S., Headlee, D. J., McCall, N. A., Samid, D., and Meyers, C. E., 1994, A phase I and pharmacokinetic study of intraveous phenylacetate in patients with cancer, Cancer Res. 54: 1690–1694.PubMedGoogle Scholar
  334. Thompson, S. L., and Krisans, S. K., 1990, Rat liver peroxisomes catalyze the initial step in cholesterol synthesis: the condensation of acetyl CoA units into acetoacetyl CoA, J. Biol. Chem. 265: 5731–5735.PubMedGoogle Scholar
  335. Toth, M. J., Park, J., and Huwyler, L., 1995, Purification of rat liver mevalonate pyrophosphate decarboxylase, FASEBJ. 9:A1293.Google Scholar
  336. Trentalance, A., Leoni, S., Mangiantini, M. T., Spagnuolo, S., Feingold, K., Hughes-Fulford, M., Siper-stein, M. D., Cooper, A. D., and Erickson, S. K., 1984, Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis and esterification during the first cell cycle of liver regeneration, Biochim. Biophys. Acta 794:142–151.PubMedCrossRefGoogle Scholar
  337. Trueblood, C. E., Ohya, Y., and Rine, J., 1993, Genetic evidence for in vivo cross-specificity of the CaaX-box protein prenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae, Mol Cell Biol. 13:4260–4275.PubMedGoogle Scholar
  338. van Blitterswijk, W. J., Emmelot, P., Hilkmann, H. A. M., Oomenmeulmans, E. P. M., and Inbar, M., 1977, Differences in lipid fluidity among isolated plasma membranes of normal and leukemic lymphocytes and membranes exfoliated from their cell surface, Biochim. Biophys. Acta 467: 309–320.PubMedCrossRefGoogle Scholar
  339. van Blitterswijk, W. J., Emmelot, P., Hilkmann, H. A. M., Higers, J., and Feltkamp, C. A., 1979, Rigid plasma membrane-derived vesicles, enriched in tumor-associated surface antigens (MLr) occurring in the ascites fluid of a murine leukemia (GRSL), Intl. J. Cancer 23:62–70.CrossRefGoogle Scholar
  340. van Blitterswijk, W. J., De Veer, G., Krol, J. H., and Emmelot, P., 1982, Comparative lipid analysis of purified plasma membranes and shed extracellular membrane vesicles from normal murine thymocytes and leukemic GRSL cells, Biochim. Biophys. Acta 688:495–504.PubMedCrossRefGoogle Scholar
  341. van Blitterswijk, W. J., Hilkmann, H., and Hengeveld, T., 1984, Differences in membrane lipid composition and fluidity of transplanted GRSL lymphoma cells, depending on their site of growth in the mouse, Biochim. Biophys. Acta 778:521–529.PubMedCrossRefGoogle Scholar
  342. van der Pyl, D., Inokoshi, J., Shiomi, K., Yang, H., Takeshima, H., and Omura, S., 1992, Inhibition of farnesyl:protein transferase by gliotoxin and acetylgliotoxin, J. Antibiot. 45:1802–1805.PubMedCrossRefGoogle Scholar
  343. van Hoeven, R., and Emmelot, P., 1972, Studies on plasma membranes. XVIII. Lipid class composition of plasma membranes isolated from rat and mouse liver and hepatomas, J. Membr. Biol. 9:105–126.PubMedCrossRefGoogle Scholar
  344. van Meer, G., 1987, Plasma membrane cholesterol pools, Trends Biochem. Sci. 12:375–376.CrossRefGoogle Scholar
  345. Vincent, T., Wulfert, E., and Merler, E., 1991, Inhibition of growth factor signaling pathways by lovastatin, Biochem. Biophys. Res. Commun. 180:1284–1289.PubMedCrossRefGoogle Scholar
  346. Vogt, A., Qian, Y., Blaskovich, M. A., Fossum, R. D., Hamilton, A. D., and Sebti, S. M., 1995, A non-peptide mimetic of Ras-CAAX: selective inhibition of farnesyltransferase and Ras processing, J. Biol. Chem. 270:660–664.PubMedCrossRefGoogle Scholar
  347. Waterman, M. R., 1995, A rising StAR: an essential role in cholesterol transport, Science 267: 1780–1781.PubMedCrossRefGoogle Scholar
  348. Watson, J. A., Havel, C. M., Lobos, D. V., Baker, F. C., and Morrow, C. J., 1985, Isoprenoid synthesis in isolated embryonic Drosophila cells, J. Biol. Chem. 260:14083–14091.PubMedGoogle Scholar
  349. Wedegaertner, P. B., Wilson, P. T., and Bourne, H. R., 1995, Lipid modifications of trimeric G proteins, J. Biol. Chem. 270:503–506.PubMedCrossRefGoogle Scholar
  350. Weibel, E. R., 1984, The Pathway for Oxygen: Structure and Function in the Mammalian Respiratory System, Harvard University Press, Cambridge, MA.Google Scholar
  351. Willumsen, B. M., Norris, K., Papageorge, A. G., Hubbert, N. L., and Lowy, D. R., 1984, Harvey murine sarcoma virus p21 ras protein: biological and biochemical significance of the cysteine nearest the carboxy terminus, EMBO J. 3:2581–2585.Google Scholar
  352. Wirtz, K. W. A., 1991, Phospholipid transfer proteins, Annu. Rev. Biochem. 60:73–99.PubMedCrossRefGoogle Scholar
  353. Wittinghofer, A., and Herrmann, C., 1995, Ras-effector interactions, the problem of specificity, FEBS Lett. 369:52–56.PubMedCrossRefGoogle Scholar
  354. Xu, Y., Mayor, J. A., Gresme, D., Wood, D., and Kaplan, R. S., 1995, High-yield bacterial expression, purification, and functional reconstitution of the tricarboxylate transport protein from rat liver mitochondria, Biochem. Biophys. Res. Commun. 207:783–789.PubMedCrossRefGoogle Scholar
  355. Yan, N., Ricca, C., Fletcher, J., Glover, T., Seizinger, B. R., and Manne, V., 1995, Farnesyltransferase inhibitors block the neurofibromatosis type I (NFI) malignant phenotype, Cancer Res. 55: 3569–3575.PubMedGoogle Scholar
  356. Yeagle, P., 1987, The Membranes of Cells, Academic Press, NY.Google Scholar
  357. Yeagle, P., 1992, The dynamics of membrane lipids, in: The Structure of Biological Membranes (P. Yeagle, ed.), pp. 157–174, CRC Press, Boca Raton, FL.Google Scholar
  358. Yeagle, P. L., 1991, Modulation of membrane function by cholesterol, Biochimie 73:1303–1310.PubMedCrossRefGoogle Scholar
  359. Ying, W., Sepp-Lorenzino, L., Cai, K., Aloise, P., and Coleman, P. S., 1994, Photoaffinity-labeling peptide substrates for farnesyl-protein transferase and the intersubunit location of the active site, J. Biol. Chem. 269:470–477.PubMedGoogle Scholar
  360. Yokoyama, K., and Gelb, M. H., 1993, Purification of a mammalian protein geranylgeranyltransferase, J. Biol. Chem. 268:4055–4060.PubMedGoogle Scholar
  361. Yokoyama, K., Goodwin, G., Ghomashchi, F., Glomset, J. A., and Gelb, M., 1991, A protein geranylgeranyltransferase from bovine brain: implications for protein prenylation specificity, Proc. Natl. Acad. Sci. USA 88:5302–5306.PubMedCrossRefGoogle Scholar
  362. Zafra, M. F., Riquelme, S., Castillo, M., and Garcia-Peregrin, E., 1987, Effect of Clofibrate on brain mevalonate-5-pyrophosphate decarboxylase, Neurochem. Res. 12:787–791.PubMedCrossRefGoogle Scholar
  363. Zhang, F., and Casey, P. J., 1996, Protein prenylation: molecular mechanisms and functional consequences, Annu. Rev. Biochem. 65:241–269.PubMedCrossRefGoogle Scholar
  364. Zhang, F. L., Diehl, R. E., Kohl, N. E., Gibbs, J. B., Giros, B., Casey, P. J., and Omer, C. A., 1994a, cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I, J. Biol. Chem. 269:3175–3180.PubMedGoogle Scholar
  365. Zhang, L., Sachs, C. W., Fine, R. L., and Casey, P. J., 1994b, Interaction of prenylcysteine methyl esters with the multidrug resistance transporter, J. Biol. Chem. 269:15973–15976.PubMedGoogle Scholar
  366. Zhang, L., Sachs, C. W., Fu, H.-W., Fine, R. L., and Casey, P. J., 1995, Characterization of prenylcys-teines that interact with P-glycoprotein and inhibit drug transport in tumor cells, J. Biol. Chem. 270:22859–22865.PubMedCrossRefGoogle Scholar
  367. Zhang, F. L., Fu, H. W., Casey, P. J., and Bishop, W. R., 1996, Substitution of cadmium for zinc in farnesyl:protein transferase alters its substrate specificity, Biochemistry 35:8166–8171.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Peter S. Coleman
    • 1
  • Li-Chuan Chen
    • 2
  • Laura Sepp-Lorenzino
    • 3
  1. 1.Laboratory of Metabolic RegulationThe Boston Biomedical Research InstituteBostonUSA
  2. 2.Clinical Pharmacology BranchNational Cancer Institute, National Institutes of HealthBethesdaUSA
  3. 3.Program in Cell Biology and Genetics and Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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