Integrated control of cell proliferation and cell death by the c-myc oncogene.
Philos Trans R Soc Lond B Biol Sci
; 345(1313): 269-75, 1994 Aug 30.
Article
en En
| MEDLINE
| ID: mdl-7846125
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)
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
División Celular
/
Regulación de la Expresión Génica
/
Genes myc
/
Apoptosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Philos Trans R Soc Lond B Biol Sci
Año:
1994
Tipo del documento:
Article
País de afiliación:
Reino Unido