Advertisement

Apoptosis/Programmed Cell Death

A Historical Perspective
  • Sudhir Gupta
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

The concept of cell death dates back to 1858, when cell death at the gross level was discussed in Virchow’s Cellular Pathology as degeneration, mortification, and necrosis equivalent to the term “gangrene”1. Carl Weigart in 1877 described coagulation necrosis in which he observed that necrotic cells lose their nuclei 2. When stains became available in 1885, Walther Flemming described spontaneous cell death as a physiological event3. This was perhaps the first morphological description of apoptosis. He observed that the epithelial lining of regressive ovarian follicles was full of cells whose nuclei were breaking up. The broken nuclei ultimately disappeared. He described half-moons of pyknotic chromatin and loose chromatin in the follicular cavity. He termed the entire process “chromatolysis”. Soon after the description of Walther Flemming, Franz Nissen, a German medical student, described chromatolysis in the lactating mammary gland4. Chromatin margination was described in 18905. In 1892, Strobe gave a detailed account of chromatolysis and nuclear pathology in breast cancer cells, which would be a modern description of apoptosis6. Ludwig Grapher in 1914 published a paper in German under the title “Eine neue Anschauung uber physiologische Zellausschaltung”, whose English translation is, “A new point of view regarding the elimination of cells”7. His hypothesis was that there must be an amitotic mechanism to counterbalance mitosis. Based upon his studies, he concluded that physiological elimination of cells occurs by chromatolysis during the shrinkage of organs; a sister cell engulfs a neighboring cell that breaks down. Glucksmann understood the significance of chromatolysis in morphogenetic mechanism. In a landmark paper, he described physiological cell death in the embryo8. In 1960 Majno et al, using a model of ischemic cell death, established a role of protein denaturation in cell death9. The concept of cell suicide was proposed by De Duve, who postulated that the cells might be killed from within by an explosion of their lysosomes acting as “suicide bag s”10.

Keywords

Programme Cell Death Ischemic Cell Death Cell Death Gene Spontaneous Cell Death Physiological Cell Death 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Virchow R. Cellular Pathology as Based Upon Physiological and Pathological Histology. Ed. 2 (translated from German by B. Chance, 1859); reproduced by Dover Publications, New York pp 356 (1971).Google Scholar
  2. 2.
    Weigert C. Uber Croup und Diphtheritis. Ein experimeteller und anatomischer Beitrag zur Pathologie der specifischen Entzundungsformen. Virchows Arch. Pathol. Anat. 72: 461 (1877–1878)Google Scholar
  3. 3.
    Flemming W. Uber die Bildung von Richtungsfiguren in Saugethiereiern beim Untergang Graaf’scher Follikel. Arch Anat EntwGesh 221 (1885).Google Scholar
  4. 4.
    Nissen F. Uber das Verhalten der Kerne in den Milchdrusenzellen bei der Absonderung. Arch Mikroskop Anat. 26: 337 (1886).CrossRefGoogle Scholar
  5. 5.
    Arnheim G. Coagulationsnekrose und Kernschwund. Virchows Arch Path. Anat. 120: 367 (1890).Google Scholar
  6. 6.
    Stobe H. Zur Kenntnis verschiedener cellularer Vorgange und Erscheinungen in Geschwulsten. Beitr. Pathol. Anat. 11: 1 (1914).Google Scholar
  7. 7.
    Grapher L. Eine neue Anschauung uber physiologische Zellausschaltung. Arch. Zellforsch 12: 373 (1914).Google Scholar
  8. 8.
    Glucksmann A. Cell death in normal vertebrate ontogeny. Biol. Rev. Camb. Philos. Soc. 26: 59 (1951).CrossRefGoogle Scholar
  9. 9.
    Majno G., La Gattuta M., Thompson T.E. Cellular death and necrosis: chemical, physical and morphologic changes in rat liver. Virchows Arch. Pathol. Anat. 333: 421 (1960).Google Scholar
  10. 10.
    Majno G. and Joris I. Cells, Tissues and Disease: Principles of General Pathology. Blackwell Science, Inc. (in press)Google Scholar
  11. 11.
    Kerr J.F.R. A histochemical study of hypertrophy and ischemic injury of rat liver with special reference to changes in lysosomes. J. Pathol. Bactriol. 90: 557 (1965).CrossRefGoogle Scholar
  12. 12.
    Kerr J.F.R. An electron-microscope study of liver cell necrosis due to heliotrine. J. Pathol. 97: 557 (1969).PubMedCrossRefGoogle Scholar
  13. 13.
    Kerr J.F.R. Shrinkage necrosis: a distinct mode of cellular death. J. Pathol. 105: 13 (1971).PubMedCrossRefGoogle Scholar
  14. 14.
    Kerr J.F.R., Wyllie A.H., and Currie A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Brit. J. Cancer 26: 239 (1972).PubMedCrossRefGoogle Scholar
  15. 15.
    Cohen L.J. and Ellis M.E. Radiation-induced changes in tissue nucleic acids: release of soluble deoxynucleotides in the spleen. Radiat. Res. 7: 508 (1957).CrossRefGoogle Scholar
  16. 16.
    Skalka M. and Matyasova J. The effect of low radiation doses on the release of deoxyribonucleotides in hematopoietic and lymphatic tissues. Int. J. Radiat. Biol. 7: 41 (1963).CrossRefGoogle Scholar
  17. 17.
    Vodolazskaya N.A. and Vermolaeva N.V. Investigation of DNP degradation produced by y-irradiation, hydrocortisone and degranol in rat thymus. Radiobiologiya 11: 335 (1971).Google Scholar
  18. 18.
    Saunders J.W. Jr. Death in embryonic systems. Science 154: 604 (1966).PubMedCrossRefGoogle Scholar
  19. 19.
    Lockshin R.A. and Williams C.W. Programmed cell death. I. Cytology of generation in the intersegmental muscles of the Pernyi Silkmoth. J. Insect Physiol. 11: 123 (1965).PubMedCrossRefGoogle Scholar
  20. 20.
    Lockshin R.A. and Williams C.M. Programmed cell death II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkworm. J. Insect Physiol. 10: 643 (1964).CrossRefGoogle Scholar
  21. 21.
    Skalka M., Matyasova J., Cejkova M. DNA in chromatin of irradiated lymphoid tissues degrades in vivo into regular fragments. FEBS Lett. 72: 271 (1976).PubMedCrossRefGoogle Scholar
  22. 22.
    Yamada T., Ohyama H., Kinjo Y., Watanabe M. Evidence for internucleosomal breakage of chromatin in rat thymocytes irradiated in vitro. Radiat. Res. 85: 544 (1981).PubMedCrossRefGoogle Scholar
  23. 23.
    Zhivotovsky B.D., Zvonareva N.B., Hanson K.P. Characteristics of rat thymus chromatin degradation products after whole body irradiation. Int. J. Rad. Biol. 39: 437 (1981).CrossRefGoogle Scholar
  24. 24.
    Wyllie A.H., Morris R.G., Smith A.L., Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J. Pathol. 142: 67–77, 1984PubMedCrossRefGoogle Scholar
  25. 25.
    Pachatnikov V.A., Afanasyev V.N., Korol B.A., Korneev V.N., Rochev Y.A., and Umansky S.R. Flow cytometry analysis of DNA degradation in thymocytes of y-irradiation or hydrocortisone treated rats. Gen. Physiol. Biophys. 5: 273 (1986).Google Scholar
  26. 26.
    Afanasyev V.N., Korol B.A., Mantsygin Y.A., Nelipovich P.A., Pechatnikov V.A. and Umansky S.R. Flow cytometry and biochemical analysis of DNA degradation characteristics of two types of cell death. FEBS Lett. 194: 347 (1986).CrossRefGoogle Scholar
  27. 27.
    Sulston J.E. and Horvitz H.R. Post embryonic lineages of the nematode Caenorhabditis elegans. Dev. Biol. 82: 110 (197 7).Google Scholar
  28. 28.
    Ellis H.M. and Horvitz H.R. Genetic control of programmed cell death in the nematode C. elegans. Cell 44: 817 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    Yuan J. and Horvitz H.R. The Caenorhabditis elegans gene Ced-3 and Ced-4 act autonomously to cause programmed cell death. Dev. Biol. 138: 33 (1990).PubMedCrossRefGoogle Scholar
  30. 30.
    Yuan J., Shaham S., Ledoux S., Ellis J.M. and Horvitz H.R. The C. elegans cell death gene Ced-3 encodes a protein similar to mammalian interleukin-lß converting enzyme. Cell 75: 641 (1993).PubMedCrossRefGoogle Scholar
  31. 31.
    Miura M., Zhu H., Rotello R., Hartwieg E.A. and Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C.elegans cell death gene ced-3. Cell 78: 653–660, 1993.CrossRefGoogle Scholar
  32. 32.
    Henkart P.A. ICE family proteases: mediators of all apoptotic cell death. Immunity 4: 195 (1996).PubMedCrossRefGoogle Scholar
  33. 33.
    Nicholson D.W., Ali A., Thornberry N.A., Vaillancourt J.P, Ding C.K., Gallant M., Gareau Y., Griffin P.R., Labelle M., Lazebnik Y.A., Munday N.A., Raju S.M., Smulson M.E., Yamin T-T., Yu V.L. and Miller D.K. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376: 37 (1995)PubMedCrossRefGoogle Scholar
  34. 34.
    Hengartner M.O., Ellis R.E. and Horvitz H.R. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356: 494 (1995).CrossRefGoogle Scholar
  35. 35.
    Hengartner M.O., and Horvitz H.R. C. elegans cell survival gene Ced-9 encodes a functional homologue of the mammalian proto-oncogene bc1–2. Cell 76: 665 (1994).PubMedCrossRefGoogle Scholar
  36. 36.
    Tsujimoto Y., Finger L.R., Yunis J., Nowell P.C. and Croce C.M. Cloning of chromosomes break point of neoplastic B cells with the t(14:18) chromosome translocation. Science 226: 1097 (1989)CrossRefGoogle Scholar
  37. 37.
    Tsujimoto Y., and Croce C.M. Analysis of structure, transcripts, and protein products of bc1–2, the gene involved in human follicular lymphoma. Proc. Natl. Acad. Sci. (USA) 83: 5214 (1985).CrossRefGoogle Scholar
  38. 38.
    Chen-Levy Z., Nourse J., and Cleary M.L. The bc1–2 candidate proto-oncogene product is a 24-kilodalton integral membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the (14:18) translocation. Mol. Cell Biol. 9: 701 (1989).PubMedGoogle Scholar
  39. 39.
    Hockenbery M.O., Nunez Z., Milliman C., Schreiber R.D., and Korsmeyer S.J. Bc1–2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334 (1990).PubMedCrossRefGoogle Scholar
  40. 40.
    Chen-Levy Z. and Cleary M.L. Membrane topology of the BcI-2 proto-oncogene protein demonstrated in vitro. J. Biol. Chem. 265: 4929 (1990).PubMedGoogle Scholar
  41. 41.
    Siegal R.M., Katsumata M., Miyashita T., Louie D.C., Greene M.I., and Reed J.C. Inhibition ofthymocyte apoptosis and negative antigenic selection in bc1–2 transgene mice. Proc. Natl. Acad. Sci. (USA) 89: 7003 (1992).CrossRefGoogle Scholar
  42. 42.
    Strasser A., Harris A.W., and Cory S. bc1–2 transgene inhibits T cell death and perturbs thymic self censorship. Cell 67: 889 (1991).PubMedCrossRefGoogle Scholar
  43. 43.
    Vox D.L., Cory S., and Adams J. Bc1–2 gene promotes haematopoietic cell survival and cooperates withc-myc to immortalize pre-B cells. Nature 335: 440 (1988).CrossRefGoogle Scholar
  44. 44.
    Nunez G., Hockenbery D., McDonnell T.J., Sorensen C.M., and Korsmeyer S.J. Bcl-2 maintains B cell memory. Nature 353: 71 (1991).PubMedCrossRefGoogle Scholar
  45. 45.
    Strasser A., Harris A.W., Corcoran L.M., and Cory S. Bcl-2 expression promotes B but not T-lymphoid development in SCID mice. Nature 368: 457 (1994).PubMedCrossRefGoogle Scholar
  46. 46.
    Takayama S., Sato T., Krajewski S., Kochel K., Irie S., Milian J. and Reed J. Cloning and functional analysis of BAG-1: a novel Bc1–2 binding protein with anti-cell death activity. Cell 80: 279 (1995).PubMedCrossRefGoogle Scholar
  47. 47.
    Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T., Turka L.A., Mao X., Nunez G., and Thompson C. bel-x, a bcl-2 related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597 (1993).PubMedCrossRefGoogle Scholar
  48. 48.
    Oltvai Z.N., Miliman C., and Korsmeyer S.J. Bcl-2 heterodimerizes in vivo with a conserved homologue, Bax, that accelerates programmed cell death. Cell 74: 609 (1993).PubMedCrossRefGoogle Scholar
  49. 49.
    Kozopas K.M., Yang T., Buchan H.L., Zhou P., and Craig R.W. MCL 1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to Bc1–2. Proc. Natl. Acad. Sci. (USA) 90: 3516 (1993).CrossRefGoogle Scholar
  50. 50.
    Lin E.Y., Orlofsky A., Berger M.S., Prystowsky. Characterization of Al, a novel hematopoetic-specific early-response gene with sequence similarity to bcl-2. J. Immunol. 151: 1979 (1993).PubMedGoogle Scholar
  51. 51.
    Yonish-Rouach E., Resnizky D., Lotem J., Sachs L., Kimchi A., and Oren M. Wild-type p53 induces apoptosis in myeloid leukemic cells that is inhibited by interleukin-6. Nature 352: 345 (1991).PubMedCrossRefGoogle Scholar
  52. 52.
    Lowe S.W., Schmitt E.M., Smith S.W., Osborne B.A., and Jacks T. p53 is required for irradiation-induced apoptosis in murine thymocytes. Nature 362: 847 (1993).PubMedCrossRefGoogle Scholar
  53. 53.
    Clarke A.R., Purdie C.A., Harrison D.J., Morris R.G., Bird C.C., Hooper M.L., and Wyllie A.H. Thymocyte apoptosis induced by p63 dependent and independent pathways. Nature 362: 849 (1993).PubMedCrossRefGoogle Scholar
  54. 54.
    Chiou S.K., Rao L., and White E. Bel-2 blocks p53-dependent apoptosis. Mol. Cell. Biol. 14: 2556 (1994).PubMedCrossRefGoogle Scholar
  55. 55.
    Miyashita T., Krajewski S., Krajewska M., Wang H.G., Lin H.K., Liebermann D.A., Hoffman B., and Reed J.C. Tumor suppressor p53 is a regulator of bc1–2 and bax gene expression in vitro and in vivo. Oncogene 9: 1799 (1994).PubMedGoogle Scholar
  56. 56.
    Miyashita T., Harigai M., Hanada M., and Reed J.C. Identification of a p53- dependent negative response element in the bc1–2 gene. Cancer Res. 54: 3131 (1994).PubMedGoogle Scholar
  57. 57.
    Shi Y., Glynn J., Guilbert L.J., Cotter T.G., Bisonette R.P., and Green D.R. Role of c-myc in activation-induced apoptotic cell death in T-cell hybridoma. Science 257: 212 (1992).PubMedCrossRefGoogle Scholar
  58. 58.
    Evan G.I., Wyllie A.H., Gilbert C.S., Lttlewood T.D., Land H., Brooks M., Waters C.M., Penn L.Z. and Hancook D.C. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119 (1992).PubMedCrossRefGoogle Scholar
  59. 59.
    Bissonnette R.P., Echeverri F., Mahboubi A., and Green D.R. Apoptotic cell death induced by c-mvc is inhibited by bel-2. Nature 359: 352 (1992).CrossRefGoogle Scholar
  60. 60.
    Fanidi A., Harrington E.A., and Evan G.I. Cooperative interaction between c-myc and bd-2 proto-oncogenes. Nature 359: 554 (1992).PubMedCrossRefGoogle Scholar
  61. 61.
    Trauth B.C., Klas C., Peters A.M.J., Matzku S., Moller P., Falk W., Debatin K.M., and Krammer P.H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245: 301 (1989).PubMedCrossRefGoogle Scholar
  62. 62.
    Yonehara S., Ishi A., and Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J. Exp. Med. 169: 1747 (1989).PubMedCrossRefGoogle Scholar
  63. 63.
    N., Yonehara S., Ishii A., Yonehara M., Mizushima S.I., Sameshima M., Hase A., Seto Y. and Nagata S. The polypeptide encoded by the eDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66: 233 (1991).Google Scholar
  64. 64.
    Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B.C., Ponsting H., and Krammer P.H. Purification and molecular cloning of the APO-I cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J. Biol. Chem. 67: 10709 (1992).Google Scholar
  65. 65.
    Watanabe-Fukunaga R., Brennan C.I., Itoh N., Yonehara S., Copeland N.G., Jenkins N.A., and Nagata S. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J. Immuno1. 148: 1274 (1992).Google Scholar
  66. 66.
    Itoh N. and Nagata S. A novel protein domain required for apoptosis.J. Biol. Chem. 268: 10932 (1993).PubMedGoogle Scholar
  67. 67.
    Tartaglia L.A., Ayres T.M., Wong G.H.W., and Goeddel D.V. A novel domain within the 55 kd TNF receptor signals cell death. Cell 74: 845 (1993).Google Scholar
  68. 68.
    Enari M., Hug H. and Nagata S. Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375: 78 (1995).PubMedCrossRefGoogle Scholar
  69. 69.
    Chennaiyan A.M., O’Rourke K., Tiwari M. and Dixit V. FADD, a novel death-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 61: 505 (1995).CrossRefGoogle Scholar
  70. 70.
    Stanger B.Z., Leder P., Lee T., Kim E., Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81: 515 (1995).CrossRefGoogle Scholar
  71. 71.
    Sato T., Irie S., Kitada S. and Reed J. FAP-1: a protein tyrosine phosphatase that associates with Fas. Science 268: 411 (1995).PubMedCrossRefGoogle Scholar
  72. 72.
    Boldin M.P., Varfoloneef E.E., Pancer Z., Mett I., Camonis J. and Wallach D. Anovel protein that interacts with the death domain of Fas/APO-1 contains a sequence motif related to the death domain. J. Biol. Chem. 270: 7795 (1995).PubMedCrossRefGoogle Scholar
  73. 73.
    Cohen P.L., and Eisenberg R.A. The 1pr and gld genes in systemic autoimmunity: Life and death in the Fas lane. Immunol. Today 13: 427 (1992).PubMedCrossRefGoogle Scholar
  74. 74.
    Wu J., Zhou T., He J. and Mountz J.D. Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J. Exp. Med. 178: 461 (1993).PubMedCrossRefGoogle Scholar
  75. 75.
    Chu J-L., Drappa J., Parnnasa A., and Elkon K.B. The defect in fas mRNA expressed in MRL/Ipr is associated with insertion of the retrotransposon, Etn. J. Exp. Med. 178: 723 (1994).CrossRefGoogle Scholar
  76. 76.
    Adachi M., Watanabe-Fukunaga R. and Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of 1pr mice. Proc. Natl. Acad. Sci. (USA) 90: 1756 (1993).CrossRefGoogle Scholar
  77. 77.
    Watanabe-Fukunaga R., Brannan C.I., Copeland N.G., Jenkins N.A., and Nagata S. Lymphopoliferation disorder in mice explained by defects in Fas antigen that mediate apoptosis. Nature 356: 314 (1992).PubMedCrossRefGoogle Scholar
  78. 78.
    Wu J., Zhou T., Zhang J., He J., Gause W.C. and Mountz J.D. Correction of accelerated autoimmune disease by early replacement of the mutated 1pr gene with the normal fas apoptosis gene in the T cells of transgenic MRL-1prRpr mice. Proc. Natl. Acad. Sci. (USA) 91: 2344 (1994).CrossRefGoogle Scholar
  79. 79.
    Suda T., Takahashi T., Golstein P., and Nagata S. Molecular cloning and expression of Fas ligand, a novel member of the tumor necrosis factor family. Cell 75: 1169 (1992).CrossRefGoogle Scholar
  80. 80.
    Takahashi T., Tanaka M., Inazawa J., Abe T., Suda T., and Nagata S. Human Fas ligand: gene structure, chromosome location and species specificity. Int. Immunol. 6: 1567 (1994).PubMedCrossRefGoogle Scholar
  81. 81.
    Suda T. and Nagata S. Purification and characterization of the Fas ligand that induces apoptosis. J. Exp. Med. 179: 873 (1994).PubMedCrossRefGoogle Scholar
  82. 82.
    Takahashi T., Tanaka M., Brannan C.I., Jenkin N.A., Copeland N.G., Suda T., and Nagata S. Generalized lymphoprolireative disease in mice, caused by a point mutation in the Fas ligand. Cell 76: 969 (1994).PubMedCrossRefGoogle Scholar
  83. 83.
    Rieux-Laucat F., Le Diest F., Hivroz C., Roberts I.A., Debatin K.M., Fischer A., and de Villartay J.P. Mutation in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268: 1347 (1995).PubMedCrossRefGoogle Scholar
  84. 84.
    Fisher G.H., Rosenberg F.J., Straus S., Dale J., Middelton L.A., Lin A.Y., Strober W., Lenardo M., and Puck J.M. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81: 935 (1995).PubMedCrossRefGoogle Scholar
  85. 85.
    Kashahara T., Wada Y., Nuda I., Ohno A., Yachie H., Seki T., Miyawaki N., and Taniguchi N. Human lymphoproliferative disease associated with FAS mutation. The FASEB J. 10 (6): A 1063, 1996Google Scholar
  86. 86.
    Liu Z.G., Smith S.W., McLaughlin K.A., Schwartz L.M. and Osborne B.A. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur 77. Nature 367: 281 (1994).PubMedCrossRefGoogle Scholar
  87. 87.
    Woronicz J.D., Calnan B., Ngo V., and Winoto A. Requirement for the orphan steroid receptor Nur77 in apoptosis of T cell hybridomas. Nature 367: 277 (1994).PubMedCrossRefGoogle Scholar
  88. 88.
    Okabe T., Takayanagi R., Imasaki K., Haji M., Nawata H., and Watnabe T. cDNA cloning of a NGF1-B/nur77-related transcription factor from an apoptotic human T cell line. J. Immunol. 154: 3871–3879, 1995.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Sudhir Gupta
    • 1
  1. 1.Division of Basic and Clinical ImmunologyUniversity of CaliforniaIrvineUSA

Personalised recommendations