Integrated control of cell proliferation and cell death by the c-myc oncogene.

G. Evan, E. Harrington, A. Fanidi, H. Land, B. Amati, M. Bennett

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Regulation of multicellular architecture involves a dynamic equilibrium between cell proliferation, differentiation with consequent growth arrest, and cell death. Apoptosis is one particular form of active cell death that is extremely rapid and characterized by auto-destruction of chromatin, cellular blebbing and condensation, and vesicularization of internal components. The c-myc proto-oncogene encodes an essential component of the cell's proliferative machinery and its deregulated expression is implicated in most neoplasms. Intriguingly, c-myc can also act as a potent inducer of apoptosis. Myc-induced apoptosis occurs only in cells deprived of growth factors or forcibly arrested with cytostatic drugs. Myc-induced apoptosis is dependent upon the level at which it is expressed and deletion mapping shows that regions of c-Myc required for apoptosis overlap with regions necessary for co-transformation, autoregulation, inhibition of differentiation, transcriptional activation and sequence-specific DNA binding. Moreover, induction of apoptosis by c-Myc requires association with c-Myc's heterologous partner, Max. All of this strongly implies that c-Myc drives apoptosis through a transcriptional mechanism: presumably by modulation of target genes. Two simple models can be invoked to explain the induction of apoptosis by c-Myc. One holds that death arises from a conflict in growth signals which is generated by the inappropriate or unscheduled expression of c-Myc under conditions that would normally promote growth arrest. In this 'Conflict' model, induction of apoptosis is not a normal function of c-Myc but a pathological manifestation of its deregulation. It thus has significance only for models of carcinogenic progression in which myc genes are invariably disrupted.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)269-275
Number of pages7
JournalPhilosophical transactions of the Royal Society of London. Series B: Biological sciences
Volume345
Issue number1313
Publication statusPublished - Aug 30 1994

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Integrated control
myc Genes
oncogenes
apoptosis
Cell proliferation
Cell death
cell death
cell proliferation
Cell Death
Cell Proliferation
Apoptosis
Growth
Genes
proto-oncogenes
autoregulation
Deregulation
gene
deregulation
Cytostatic Agents
transcriptional activation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

Cite this

Integrated control of cell proliferation and cell death by the c-myc oncogene. / Evan, G.; Harrington, E.; Fanidi, A.; Land, H.; Amati, B.; Bennett, M.

In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences, Vol. 345, No. 1313, 30.08.1994, p. 269-275.

Research output: Contribution to journalArticle

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