The retinoblastoma protein and its homolog p130 regulate the G1/S transition in pancreatic beta-cells.
Diabetes
; 58(8): 1852-62, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19509021
ABSTRACT
OBJECTIVE:
The retinoblastoma protein family (pRb, p130, p107) plays a central role in the regulation of cell cycle progression. Surprisingly, loss of pRb in the beta-cell has no discernible effect on cell cycle control. Therefore, we explored the effects of individual loss of either p130 or p107 in addition to the simultaneous loss of both pRb/p130 on the beta-cell. RESEARCH DESIGN ANDMETHODS:
Adult mice deficient in either p130 or p107 or both pRb/p130 were examined for effects on beta-cell replication, function, and survival. The Cre-Lox system was also used to inactivate pRb in wild-type and p130-deficient beta-cells in vitro.RESULTS:
In vivo loss of either p107 or p130 did not affect beta-cell replication or function. Combined pRb/p130 loss, however, resulted in dramatically accelerated proliferation as well as apoptotic cell death. Pancreas and beta-cell mass were significantly reduced in double mutants. Despite this, overall glucose tolerance was normal, except for mild postprandial hyperglycemia. Ex vivo, acute deletion of pRb in p130-deficient beta-cells also caused a striking increase in proliferation. The combined deletion of pRb/p130 upregulated islet expression of E2F2 but not E2F1.CONCLUSIONS:
These studies define an essential role for the pocket proteins in controlling the G(1)/S transition in beta-cells. When deficient in both pRb and p130, beta-cells undergo unrestrained cell cycle reentry and activation of apoptosis. These studies underscore the central role of the pRb pathway in controlling beta-cell turnover and provide new cellular targets for beta-cell regeneration.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ciclo Celular
/
Fase G1
/
Proteína do Retinoblastoma
/
Fase S
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Células Secretoras de Insulina
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Proteína p107 Retinoblastoma-Like
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Proteína p130 Retinoblastoma-Like
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos