Control of the reversibility of cellular quiescence by the transcriptional repressor HES1.
Science
; 321(5892): 1095-100, 2008 Aug 22.
Article
en En
| MEDLINE
| ID: mdl-18719287
ABSTRACT
The mechanisms by which quiescent cells, including adult stem cells, preserve their ability to resume proliferation after weeks or even years of cell cycle arrest are not known. We report that reversibility is not a passive property of nondividing cells, because enforced cell cycle arrest for a period as brief as 4 days initiates spontaneous, premature, and irreversible senescence. Increased expression of the gene encoding the basic helix-loop-helix protein HES1 was required for quiescence to be reversible, because HES1 prevented both premature senescence and inappropriate differentiation in quiescent fibroblasts. In some human tumors, the HES1 pathway was activated, which allowed these cells to evade differentiation and irreversible cell cycle arrest. We conclude that HES1 safeguards against irreversible cell cycle exit both during normal cellular quiescence and pathologically in the setting of tumorigenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Ciclo Celular
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Proteínas de Homeodominio
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Proliferación Celular
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos