Journal of Molecular Medicine

, Volume 81, Issue 9, pp 536–548 | Cite as

Not just for housekeeping: protein initiation and elongation factors in cell growth and tumorigenesis

  • Sarah Thornton
  • Nisha Anand
  • Dan Purcell
  • Jonathan Lee
Invited Review

Abstract

Proteins provide the structural framework of a cell and perform the enzymatic activities sustaining DNA replication and energy production. The hormones and growth factors that facilitate organ-to-organ communication are proteins as are the receptors and signaling intermediaries that integrate extracellular stimuli to intracellular action. As such, eukaryotic cells devote tremendous effort and energy to protein synthesis. The enzymes involved in protein synthesis have traditionally been described as cellular housekeepers. This was meant to imply that while they were necessary for cell viability, they were not thought to have a causal role in activating cell differentiation or neoplastic development the way that a transcription factor or hormone receptor might. However, two protein translation factors, protein initiation factor eIF4E and protein elongation factor eEF1A2, have been identified as important human oncogenes. This review summarizes recent work showing that protein initiation and elongation factors have important regulatory roles in cell growth, apoptosis, and tumorigenesis.

Keywords

Cancer Protein translation Protein elongation Apoptosis Oncogene 

Abbreviations

eEF

Eukaryotic elongation factor

eIF1

Eukaryotic initiation factor

eRF

Eukaryotic release factor

PKC

Protein kinase C

PMA

Phorbol 12-myristate 13-acetate

PTI

Prostate tumor inducing

UTR

Untranslated region

References

  1. 1.
    Lockhart DJ, Winzeler EA (2000) Genomics, gene expression and DNA arrays. Nature 405:827–836CrossRefPubMedGoogle Scholar
  2. 2.
    Slonim DK (2002) From patterns to pathways: gene expression data analysis comes of age. Nat Genet 32 [Suppl]:502–508Google Scholar
  3. 3.
    Wu TD (2001) Analysing gene expression data from DNA microarrays to identify candidate genes. J Pathol 195:53–65CrossRefPubMedGoogle Scholar
  4. 4.
    Kaech SM, Hemby S, Kersh E, Ahmed R (2002) Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111:837–851PubMedGoogle Scholar
  5. 5.
    Chen ZY, Corey DP (2002) Understanding inner ear development with gene expression profiling. J Neurobiol 53:276–285CrossRefPubMedGoogle Scholar
  6. 6.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedGoogle Scholar
  7. 7.
    Alon U, Barkai N, Notterman DA, Gish K, Ybarra S, Mack D, Levine AJ (1999) Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA 96:6745–6750PubMedGoogle Scholar
  8. 8.
    Tew KD, Monks A, Barone L, Rosser D, Akerman G, Montali JA, Wheatley JB, Schmidt DE. Jr (1996) Glutathione-associated enzymes in the human cell lines of the National Cancer Institute Drug Screening Program. Mol Pharmacol 50:149–159PubMedGoogle Scholar
  9. 9.
    Chen G, Gharib TG, Huang CC, Taylor JM, Misek DE, Kardia SL, Giordano TJ, Iannettoni MD, Orringer MB, Hanash SM, Beer DG (2002) Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics 1:304–313CrossRefPubMedGoogle Scholar
  10. 10.
    Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19:1720–1730PubMedGoogle Scholar
  11. 11.
    Futcher B, Latter GI, Monardo P, McLaughlin CS, Garrels JI (1999) A sampling of the yeast proteome. Mol Cell Biol 19:7357–7368PubMedGoogle Scholar
  12. 12.
    Hershko, A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479PubMedGoogle Scholar
  13. 13.
    Hershey JW, Miyamoto S (2000) Translational control and cancer. In: Sonenberg N, Hershey JW, Mathews MB (eds) Translational control of gene expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 655–670Google Scholar
  14. 14.
    Blume-Jensen, P, Hunter T (2001) Oncogenic kinase signalling. Nature 411:355–365Google Scholar
  15. 15.
    Darnell JE Jr (2002) Transcription factors as targets for cancer therapy. Nat Rev Cancer 2:740–749CrossRefPubMedGoogle Scholar
  16. 16.
    Hahn WC, Weinberg RA (2001) Modelling the molecular circuitry of cancer. Nat Rev Cancer 2:331–341CrossRefGoogle Scholar
  17. 17.
    Fatica, A, Tollervey D (2002) Making ribosomes. Curr Opin Cell Biol 14:313–318CrossRefPubMedGoogle Scholar
  18. 18.
    Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440PubMedGoogle Scholar
  19. 19.
    Alon U, Barkai N, Notterman DA, Gish K, Ybarra S, Mack D, Levine AJ (1999) Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA 96:6745–6750PubMedGoogle Scholar
  20. 20.
    Ferrari S, Manfredini R, Tagliafico E, Rossi E, Donelli A, Torelli G, Torelli U (1990) Noncoordinated expression of S6, S11, and S14 ribosomal protein genes in leukemic blast cells. Cancer Res 50:5825–5828PubMedGoogle Scholar
  21. 21.
    Uechi T, Tanaka T, Kenmochi N (2001) A complete map of the human ribosomal protein genes: assignment of 80 genes to the cytogenetic map and implications for human disorders. Genomics 72:223–230CrossRefPubMedGoogle Scholar
  22. 22.
    Naora H, Takai I, Adachi M (1998) Altered cellular responses by varying expression of a ribosomal protein gene: sequential coordination of enhancement and suppression of ribosomal protein S3a gene expression induces apoptosis. J Cell Biol 141:741–753CrossRefPubMedGoogle Scholar
  23. 23.
    Ruggero, D, Pandolfi PP (2003) Does the ribosome translate cancer? Nat Rev Cancer 3:179–192Google Scholar
  24. 24.
    Zhang L, Zhou W, Velculescu VE, Kern SE, Hruban RH, Hamilton SR, Vogelstein B, Kinzler KW (1997) Gene expression profiles in normal and cancer cells. Science 276:1268–1272Google Scholar
  25. 25.
    Mathews MB, Sonenberg N, Hershey JW (2000) Origins and principles of translational control. In: Sonenberg N, Hershey JW, Mathews MB (eds) Translational control of gene expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 1–31Google Scholar
  26. 26.
    Hershey JW, Merrick WC (2000) The pathway and mechanism of initiation of protein synthesis. In: Sonenberg N, Hershey JW, Mathews MB (eds) Translational control of gene expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 33–88Google Scholar
  27. 27.
    Browne GJ, Proud CG (2002) Regulation of peptide-chain elongation in mammalian cells. Eur J Biochem 269:5360–5368CrossRefPubMedGoogle Scholar
  28. 28.
    Welch EM, Wang W, Peltz PW (2000) The pathway and mechanism of initiation of protein synthesis. In: Sonenberg N, Hershey JW, Mathews MB (eds) Translational control of gene expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 467–486Google Scholar
  29. 29.
    Cristofalo VJ, Pignolo RJ (1993) Replicative senescence of human fibroblast-like cells in culture. Physiol Rev 73:617–638PubMedGoogle Scholar
  30. 30.
    Lazaris-Karatzas A, Montine KS, Sonenberg N (1990) Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature 345:544–547CrossRefPubMedGoogle Scholar
  31. 31.
    Lazaris-Karatzas A, Smith MR, Frederickson RM, Jaramillo ML, Liu YL, Kung HF, Sonenberg N (1992) Ras mediates translation initiation factor 4E-induced malignant transformation. Genes Dev 6:1631–1642PubMedGoogle Scholar
  32. 32.
    Li BD, Liu L, Dawson M, De Benedetti A (1997) Overexpression of eukaryotic initiation factor 4E (eIF4E) in breast carcinoma. Cancer 79:2385–2390CrossRefPubMedGoogle Scholar
  33. 33.
    Berkel HJ, Turbat-Herrera EA, Shi R, De Benedetti A (2001) Expression of the translation initiation factor eIF4E in the polyp-cancer sequence in the colon. Cancer Epidemiol Biomarkers Prev 10:663–666PubMedGoogle Scholar
  34. 34.
    Nathan CA, Sanders K, Abreo FW, Nassar R, Glass J (2000) Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications. Cancer Res 60:3599–3604PubMedGoogle Scholar
  35. 35.
    Haydon MS, Googe JD, Sorrells DS, Ghali GE, Li BD (2000) Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck. Cancer 88:2803–2810CrossRefPubMedGoogle Scholar
  36. 36.
    Crew JP, Fuggle S, Bicknell R, Cranston DW, De Benedetti A, Harris AL (2000) Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression. Br J Cancer 82:161–166CrossRefPubMedGoogle Scholar
  37. 37.
    Rosenwald IB, Hutzler MJ, Wang S, Savas L, Fraire AE (2001) Expression of eukaryotic translation initiation factors 4E and 2alpha is increased frequently in bronchioloalveolar but not in squamous cell carcinomas of the lung. Cancer 92:2164–2171CrossRefPubMedGoogle Scholar
  38. 38.
    Balsara BR, Sonoda G, du, Manoir S, Siegfried JM, Gabrielson E, Testa JR (1997) Comparative genomic hybridization analysis detects frequent, often high-level, overrepresentation of DNA sequences at 3q, 5p, 7p, and 8q in human non-small cell lung carcinomas. Cancer Res 57:2116–2120PubMedGoogle Scholar
  39. 39.
    Sorrells DL, Meschonat C, Black D, Li BD (1999) Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor. J Surg Res 85:37–42CrossRefPubMedGoogle Scholar
  40. 40.
    Sorrells DL, Black DR, Meschonat C, Rhoads R, De Benedetti A, Gao M, Williams BJ, Li BD (1998) Detection of eIF4E gene amplification in breast cancer by competitive PCR. Ann Surg Oncol 5:232–237PubMedGoogle Scholar
  41. 41.
    Li BD, Gruner JS, Abreo F, Johnson LW, Yu H, Nawas S, McDonald JC, DeBenedetti A (2002) Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome. Ann Surg 235:732–738CrossRefPubMedGoogle Scholar
  42. 42.
    Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H, Okayama H (1992) Elongation factor-1 alpha gene determines susceptibility to transformation. Nature 359:333–336CrossRefPubMedGoogle Scholar
  43. 43.
    Liang, P, Pardee AB (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967–971PubMedGoogle Scholar
  44. 44.
    Shen R, Su ZZ, Olsson CA, Fisher PB (1995) Identification of the human prostatic carcinoma oncogene PTI-1 by rapid expression cloning and differential RNA display. Proc Natl Acad Sci USA 92:6778–6782PubMedGoogle Scholar
  45. 45.
    Su Z, Goldstein NI, Fisher PB (1998) Antisense inhibition of the PTI-1 oncogene reverses cancer phenotypes. Proc Natl Acad Sci USA 95:1764–1769CrossRefPubMedGoogle Scholar
  46. 46.
    Anand N, Murthy S, Amann G, Wernick M, Porter LA, Cukier IH, Collins C, Gray JW, Diebold J, Demetrick DJ, Lee JM (2002) Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nat Genet 31:301–305PubMedGoogle Scholar
  47. 47.
    Lee S, Francoeur AM, Liu S, Wang E (1992) Tissue-specific expression in mammalian brain, heart, and muscle of S1, a member of the elongation factor-1 alpha gene family. J Biol Chem 267:24064–24068PubMedGoogle Scholar
  48. 48.
    Knudsen SM, Frydenberg J, Clark BF, Leffers H (1993) Tissue-dependent variation in the expression of elongation factor-1 alpha isoforms: isolation and characterisation of a cDNA encoding a novel variant of human elongation-factor 1 alpha. Eur J Biochem 215:549–554PubMedGoogle Scholar
  49. 49.
    Knudsen SM, Frydenberg J, Clark BF, Leffers H (1993) Tissue-dependent variation in the expression of elongation factor-1 alpha isoforms: isolation and characterisation of a cDNA encoding a novel variant of human elongation-factor 1 alpha. Eur J Biochem 215:549–554PubMedGoogle Scholar
  50. 50.
    Lund A, Knudsen SM, Vissing H, Clark B, Tommerup N (1996) Assignment of human elongation factor 1alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3. Genomics 36:359–361CrossRefPubMedGoogle Scholar
  51. 51.
    Kallioniemi A, Kallioniemi OP, Piper J, Tanner M, Stokke T, Chen L, Smith HS, Pinkel D, Gray JW, Waldman FM (1994) Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci USA 91:2156–2160PubMedGoogle Scholar
  52. 52.
    Tanner MM, Tirkkonen M, Kallioniemi A, Collins C, Stokke T, Karhu R, Kowbel D, Shadravan F, Hintz M, Kuo WL (1994) Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. Cancer Res 54:4257–4260PubMedGoogle Scholar
  53. 53.
    Tanner MM, Tirkkonen M, Kallioniemi A, Isola J, Kuukasjarvi T, Collins C, Kowbel D, Guan XY, Trent J, Gray JW, Meltzer P, Kallioniemi OP (1996) Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer. Cancer Res 56:3441–3445PubMedGoogle Scholar
  54. 54.
    Tanner MM, Grenman S, Koul A, Johannsson O, Meltzer P, Pejovic T, Borg A, Isola JJ (2000) Frequent amplification of chromosomal region 20q12–q13 in ovarian cancer. Clin Cancer Res 6:1833–1839PubMedGoogle Scholar
  55. 55.
    Suehiro Y, Sakamoto M, Umayahara K, Iwabuchi H, Sakamoto H, Tanaka N, Takeshima N, Yamauchi K, Hasumi K, Akiya T, Sakunaga H, Muroya T, Numa F, Kato H, Tenjin Y, Sugishita T (2000) Genetic aberrations detected by comparative genomic hybridization in ovarian clear cell adenocarcinomas. Oncology 59:50–56CrossRefPubMedGoogle Scholar
  56. 56.
    Diebold J, Mosinger K, Peiro G, Pannekamp U, Kaltz C, Baretton GB, Meier W, Lohrs U (2000) 20q13 and cyclin D1 in ovarian carcinomas. Analysis by fluorescence in situ hybridization. J Pathol 190:564–571CrossRefPubMedGoogle Scholar
  57. 57.
    Tanner MM, Tirkkonen M, Kallioniemi A, Holli K, Collins C, Kowbel D, Gray JW, Kallioniemi OP, Isola J (1995) Amplification of chromosomal region 20q13 in invasive breast cancer: prognostic implications. Clin Cancer Res 1:1455–1461PubMedGoogle Scholar
  58. 58.
    Isola JJ, Kallioniemi OP, Chu LW, Fuqua SA, Hilsenbeck SG, Osborne CK, Waldman FM (1995) Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am J Pathol 147:905–911PubMedGoogle Scholar
  59. 59.
    Shlomit R, Ayala AG, Michal D, Ninett A, Frida S, Boleslaw G, Gad B, Gideon R, Shlomi C (2000) Gains and losses of DNA sequences in childhood brain tumors analyzed by comparative genomic hybridization. Cancer Genet Cytogenet 121:67–72CrossRefPubMedGoogle Scholar
  60. 60.
    Verhagen PC, Hermans KG, Brok MO, van Weerden WM, Tilanus MG, de Weger RA, Boon TA, Trapman J (2002) Deletion of chromosomal region 6q14–16 in prostate cancer. Int J Cancer 102:142–147CrossRefPubMedGoogle Scholar
  61. 61.
    Nathrath MH, Kuosaite V, Rosemann M, Kremer M, Poremba C, Wakana S, Yanagi M, Nathrath WB, Hofler H, Imai K, Atkinson MJ (2002) Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man. Oncogene 21:5975–5980CrossRefPubMedGoogle Scholar
  62. 62.
    Fu W, Bubendorf L, Willi N, Moch H, Mihatsch MJ, Sauter G, Gasser TC (2000) Genetic changes in clinically organ-confined prostate cancer by comparative genomic hybridization. Urology 56:880–885CrossRefPubMedGoogle Scholar
  63. 63.
    Grant AG, Flomen RM, Tizard ML, Grant DA (1992) Differential screening of a human pancreatic adenocarcinoma lambda gt11 expression library has identified increased transcription of elongation factor EF-1 alpha in tumour cells. Int J Cancer 50:740–745PubMedGoogle Scholar
  64. 64.
    Xie D, Jauch A, Miller CW, Bartram CR, Koeffler HP (2002) Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization. Int J Oncol 21:499–507PubMedGoogle Scholar
  65. 65.
    Mohler JL, Morris TL, Ford OH, Alvey RF, Sakamoto C, Gregory CW (2002) Identification of differentially expressed genes associated with androgen-independent growth of prostate cancer. Prostate 51:247–255CrossRefPubMedGoogle Scholar
  66. 66.
    Wit NJ de, Burtscher HJ, Weidle UH, Ruiter DJ, van Muijen GN (2002) Differentially expressed genes identified in human melanoma cell lines with different metastatic behaviour using high density oligonucleotide arrays. Melanoma Res 12:57–69CrossRefPubMedGoogle Scholar
  67. 67.
    Johnsson A, Zeelenberg I, Min Y, Hilinski J, Berry C, Howell SB, Los G (2000) Identification of genes differentially expressed in association with acquired cisplatin resistance. Br J Cancer 83:1047–1054CrossRefPubMedGoogle Scholar
  68. 68.
    Phillips SM, Bendall AJ, Ramshaw IA (1990) Isolation of gene associated with high metastatic potential in rat mammary adenocarcinomas. J Natl Cancer Inst 82:199–203PubMedGoogle Scholar
  69. 69.
    Edmonds BT, Wyckoff J, Yeung YG, Wang Y, Stanley ER, Jones J, Segall J, Condeelis J (1996) Elongation factor-1 alpha is an overexpressed actin binding protein in metastatic rat mammary adenocarcinoma. J Cell Sci 109:2705–2714PubMedGoogle Scholar
  70. 70.
    Cavallius J, Rattan SI, Clark BF (1986) Changes in activity and amount of active elongation factor 1 alpha in aging and immortal human fibroblast cultures. Exp Gerontol 21:149–157CrossRefPubMedGoogle Scholar
  71. 71.
    Blazejowski CA, Webster GC (1984) Effect of age on peptide chain initiation and elongation in preparations from brain, liver, kidney and skeletal muscle of the C57B1/6\J mouse. Mech Ageing Dev 25:323–333CrossRefPubMedGoogle Scholar
  72. 72.
    Webster GC, Webster SL (1984) Specific disappearance of translatable messenger RNA for elongation factor one in aging Drosophila melanogaster. Mech Ageing Dev 24:335–342CrossRefPubMedGoogle Scholar
  73. 73.
    Webster GC, Webster SL (1983) Decline in synthesis of elongation factor one (EF-1) precedes the decreased synthesis of total protein in aging Drosophila melanogaster. Mech Ageing Dev 22:121–128CrossRefPubMedGoogle Scholar
  74. 74.
    Shepherd JC, Walldorf U, Hug P, Gehring WJ (1989) Fruit flies with additional expression of the elongation factor EF-1 alpha live longer. Proc Natl Acad Sci U S A 86:7520–7521PubMedGoogle Scholar
  75. 75.
    Stearns SC, Kaiser M (1993) The effects of enhanced expression of elongation factor EF-1 alpha on lifespan in Drosophila melanogaster. IV. A summary of three experiments. Genetica 91:167–182PubMedGoogle Scholar
  76. 76.
    Shikama N, Ackermann R, Brack C (1994) Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster. Proc Natl Acad Sci USA 91:4199–4203PubMedGoogle Scholar
  77. 77.
    Hassell JA, Engelhardt DL (1976) The regulation of protein synthesis in animal cells by serum factors. Biochemistry 15:1375–1381PubMedGoogle Scholar
  78. 78.
    Hershey JW (1991) Translational control in mammalian cells. Annu Rev Biochem 60:717–755CrossRefPubMedGoogle Scholar
  79. 79.
    Kimball SR, Vary TC, Jefferson LS (1994) Regulation of protein synthesis by insulin. Annu Rev Physiol 56:321–348CrossRefPubMedGoogle Scholar
  80. 80.
    Morley SJ, Traugh JA (1993) Stimulation of translation in 3T3-L1 cells in response to insulin and phorbol ester is directly correlated with increased phosphate labelling of initiation factor (eIF-) 4F and ribosomal protein S6. Biochimie 75:985–989CrossRefPubMedGoogle Scholar
  81. 81.
    Chang YW, Traugh JA (1997) Phosphorylation of elongation factor 1 and ribosomal protein S6 by multipotential S6 kinase and insulin stimulation of translational elongation. J Biol Chem 272:28252–28257CrossRefPubMedGoogle Scholar
  82. 82.
    Chang YW, Traugh JA (1997) Phosphorylation of elongation factor 1 and ribosomal protein S6 by multipotential S6 kinase and insulin stimulation of translational elongation. J Biol Chem 272:28252–28257CrossRefPubMedGoogle Scholar
  83. 83.
    Venema RC, Peters HI, Traugh JA (1991) Phosphorylation of elongation factor 1 (EF-1) and valyl-tRNA synthetase by protein kinase C and stimulation of EF-1 activity. J Biol Chem 266:12574–12580PubMedGoogle Scholar
  84. 84.
    Venema RC, Peters HI, Traugh JA (1991) Phosphorylation of valyl-tRNA synthetase and elongation factor 1 in response to phorbol esters is associated with stimulation of both activities. J Biol Chem 266:11993–11998PubMedGoogle Scholar
  85. 85.
    Peters HI, Chang YW, Traugh JA (1995) Phosphorylation of elongation factor 1 (EF-1) by protein kinase C stimulates GDP/GTP-exchange activity. Eur J Biochem 234:550–556PubMedGoogle Scholar
  86. 86.
    Carr-Schmid A, Valente L, Loik VI, Williams T, Starita LM, Kinzy TG (1999) Mutations in elongation factor 1beta, a guanine nucleotide exchange factor, enhance translational fidelity. Mol Cell Biol 19:5257–5266PubMedGoogle Scholar
  87. 87.
    Schuhmacher M, Staege MS, Pajic A, Polack A, Weidle UH, Bornkamm GW, Eick D, Kohlhuber F (1999) Control of cell growth by c-Myc in the absence of cell division. Curr Biol 9:1255–1258CrossRefPubMedGoogle Scholar
  88. 88.
    Joseph P, Lei YX, Whong WZ, Ong TM (2002) Oncogenic potential of mouse translation elongation factor-1 delta, a novel cadmium-responsive proto-oncogene. J Biol Chem 277:6131–6136CrossRefPubMedGoogle Scholar
  89. 89.
    Shuda M, Kondoh N, Tanaka K, Ryo A, Wakatsuki T, Hada A, Goseki N, Igari T, Hatsuse K, Aihara T, Horiuchi S, Shichita M, Yamamoto N, Yamamoto M (2000) Enhanced expression of translation factor mRNAs in hepatocellular carcinoma. Anticancer Res 20:2489–2494PubMedGoogle Scholar
  90. 90.
    Mimori K, Mori M, Tanaka S, Akiyoshi T, Sugimachi K (1995) The overexpression of elongation factor 1 gamma mRNA in gastric carcinoma. Cancer 75:1446–1449PubMedGoogle Scholar
  91. 91.
    Mimori K, Mori M, Inoue H, Ueo H, Mafune K, Akiyoshi T, Sugimachi K (1996) Elongation factor 1 gamma mRNA expression in oesophageal carcinoma. Gut 38:66–70PubMedGoogle Scholar
  92. 92.
    Condeelis J (1995) Elongation factor 1 alpha, translation and the cytoskeleton. Trends Biochem Sci 20:169–170PubMedGoogle Scholar
  93. 93.
    Ohta K, Toriyama M, Miyazaki M, Murofushi H, Hosoda S, Endo S, Sakai H (1990) The mitotic apparatus-associated 51-kDa protein from sea urchin eggs is a GTP-binding protein and is immunologically related to yeast polypeptide elongation factor 1 alpha. J Biol Chem 265:3240–3247PubMedGoogle Scholar
  94. 94.
    Carvalho MD, Carvalho JF, Merrick WC (1984) Biological characterization of various forms of elongation factor 1 from rabbit reticulocytes. Arch Biochem Biophys 234:603–611PubMedGoogle Scholar
  95. 95.
    Dharmawardhane S, Demma M, Yang F, Condeelis J (1991) Compartmentalization and actin binding properties of ABP-50: the elongation factor-1 alpha of Dictyostelium. Cell Motil Cytoskeleton 20:279–288PubMedGoogle Scholar
  96. 96.
    Yang F, Demma M, Warren V, Dharmawardhane S, Condeelis J (1990) Identification of an actin-binding protein from Dictyostelium as elongation factor 1a. Nature 347:494–496Google Scholar
  97. 97.
    Yang W, Burkhart W, Cavallius J, Merrick WC, Boss WF (1993) Purification and characterization of a phosphatidylinositol 4-kinase activator in carrot cells. J Biol Chem 268:392–398PubMedGoogle Scholar
  98. 98.
    Murray JW, Edmonds BT, Liu G, Condeelis J (1996) Bundling of actin filaments by elongation factor 1 alpha inhibits polymerization at filament ends. J Cell Biol 135:1309–1321PubMedGoogle Scholar
  99. 99.
    Edmonds BT, Bell A, Wyckoff J, Condeelis J, Leyh TS (1998) The effect of F-actin on the binding and hydrolysis of guanine nucleotide by Dictyostelium elongation factor 1A. J Biol Chem 273:10288–10295CrossRefPubMedGoogle Scholar
  100. 100.
    Liu G, Tang J, Edmonds BT, Murray J, Levin S, Condeelis J (1996) F-actin sequesters elongation factor 1alpha from interaction with aminoacyl-tRNA in a pH-dependent reaction. J Cell Biol 135:953–963PubMedGoogle Scholar
  101. 101.
    Shiina N, Gotoh Y, Kubomura N, Iwamatsu A, Nishida E (1994) Microtubule severing by elongation factor 1 alpha. Science 266:282–285PubMedGoogle Scholar
  102. 102.
    Moore RC, Durso NA, Cyr RJ (1998) Elongation factor-1alpha stabilizes microtubules in a calcium/calmodulin-dependent manner. Cell Motil Cytoskeleton 41:168–180CrossRefPubMedGoogle Scholar
  103. 103.
    Shultz LD, Sweet HO, Davisson MT, Coman DR (1982) 'Wasted', a new mutant of the mouse with abnormalities characteristic to ataxia telangiectasia. Nature 297:402–404PubMedGoogle Scholar
  104. 104.
    Woloschak GE, Rodriguez M, Krco CJ (1987) Characterization of immunologic neuropathologic abnormalities in wasted mice. J Immunol 138:2493–2499PubMedGoogle Scholar
  105. 105.
    Padilla M, Libertin C, Krco C, Woloschak GE (1990) Radiation sensitivity of T-lymphocytes from immunodeficient "wasted" mice. Cell Immunol 130:186–194PubMedGoogle Scholar
  106. 106.
    Goldowitz D, Shipman PM, Porter JF, Schmidt RR (1985) Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, "wasted." J Immunol 135:1806–1812Google Scholar
  107. 107.
    Potter M, Bernstein A, Lee JM (1998) The wst gene regulates multiple forms of thymocyte apoptosis. Cell Immunol 188:111–117CrossRefPubMedGoogle Scholar
  108. 108.
    Rotman, G, Shiloh Y (1998) ATM: from gene to function. Hum Mol Genet 7:1555–1563CrossRefPubMedGoogle Scholar
  109. 109.
    Chambers DM, Peters J, Abbott CM (1998) The lethal mutation of the mouse wasted (wst) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1alpha, encoded by the Eef1a2 gene. Proc Natl Acad Sci U S A 95:4463–4468CrossRefPubMedGoogle Scholar
  110. 110.
    Talapatra S, Wagner JD, Thompson CB (2001) Elongation factor-1 alpha is a selective regulator of growth factor withdrawal and ER stress-induced apoptosis. Cell Death Differ 9:856–861CrossRefGoogle Scholar
  111. 111.
    Ruest LB, Marcotte R, Wang E (2002) Peptide elongation factor eEF1A-2/S1 expression in cultured differentiated myotubes and its protective effect against caspase-3-mediated apoptosis. J Biol Chem 277:5418–5425CrossRefPubMedGoogle Scholar
  112. 112.
    Sonenberg N (1993) Translation factors as effectors of cell growth and tumorigenesis. Curr Opin Cell Biol 5:955–960PubMedGoogle Scholar
  113. 113.
    Kozak M (1991) An analysis of vertebrate mRNA sequences: intimations of translational control J Cell Biol 115:887–903Google Scholar
  114. 114.
    Johnston GC, Pringle JR, Hartwell LH (1977) Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp Cell Res 105:79–98PubMedGoogle Scholar
  115. 115.
    Huang, S, Houghton PJ (2002) Inhibitors of mammalian target of rapamycin as novel antitumor agents: from bench to clinic. Curr Opin Investig Drugs 3:295–304PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Sarah Thornton
    • 1
  • Nisha Anand
    • 1
  • Dan Purcell
    • 1
  • Jonathan Lee
    • 1
    • 2
  1. 1.Hamilton Regional Cancer CentreHamiltonCanada
  2. 2.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada

Personalised recommendations