Promotion and Inhibition of Activation‐Induced Apoptosis in T‐Cell Hybridomas by Oncogenes and Related Signals
- 1 December 1994
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 142 (1), 321-342
- https://doi.org/10.1111/j.1600-065x.1994.tb00895.x
Abstract
The Two Signal: Death/Survival Model suggests that cellular proliferation and physiological cell death should be intimately associated such that, in the absence of external influences, a normal cell departing from rest will have an equal probability of undergoing either process. The c-Myc protooncogene product has been implicated in cell cycle progression and in the control of gene expression, and more recently c-Myc has also been seen to promote apoptotic cell death. As predicted from the model, c-Myc-induced apoptosis is inhibited by growth factors or other anti-apoptotic signals including those provided by some oncogenes. Here, we discuss experiments that test the Two Signal: Death/Survival Model in the phenomenon of activation-induced apoptosis in T-cell hybridomas. Ligation of the antigen receptor on these cells leads to activation, resulting in cytokine production and apoptosis. Inhibition of c-Myc expression by addition of antisense oligodeoxynucleotides or transforming growth factor beta inhibits this form of apoptosis. Because c-Myc is known to bind to several cellular proteins, including Max, we further examined the effects of expression of a dominant negative Max on activation-induced apoptosis. We found that this Max mutant, which interferes with the function of the Myc/Max heterodimer, inhibits the induction of apoptosis by antigen receptor ligation. Thus, both Myc and Max play roles in activation-induced apoptosis, presumably via control of gene expression. Further, as predicted, signals generated from growth factor receptors or the v-Abl oncogene interfere with activation-induced apoptosis. In contrast, the anti-apoptotic effects of Bcl-2 are not active in this form of apoptosis. Finally, a role for Fas/Fas-ligand interactions in activation-induced apoptosis is considered.Keywords
This publication has 74 references indexed in Scilit:
- Premature p34 cdc2 Activation Required for ApoptosisScience, 1994
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- Induction of apoptosis by transforming growth factor-β1 in the rat hepatoma cell line MCA-RH7777: A possible association with tissue transglutaminase expressionHepatology, 1993
- Direct role for Myc in transcription initiation mediated by interactions with TFII-INature, 1993
- Bcl-2: a repressor of lymphocyte deathImmunology Today, 1992
- Bcl-2 prevents death of factor-deprived cells but fails to prevent apoptosis in targets of cell mediated killingInternational Immunology, 1992
- Alternative Forms of Max as Enhancers or Suppressors of Myc-Ras CotransformationScience, 1992
- Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populationsCell, 1991
- Cell dysfunction and depletion in AIDS: the programmed cell death hypothesisImmunology Today, 1991
- Sequence-Specific DNA Binding by the c-Myc ProteinScience, 1990