An indirect role for ASPP1 in limiting p53-dependent p21 expression and cellular senescence.
EMBO J
; 31(2): 471-80, 2012 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-22068052
ABSTRACT
In addition to acting as a transcriptional cofactor for p53, ASPP1 has been shown to function in the cytoplasm to regulate the nuclear localization and activity of YAP/TAZ. We show here that the ability of ASPP1 to activate YAP results in the decreased expression of LATS2, which lowers the ability of p53 to induce p21, cell-cycle arrest and senescence. ASPP1 expression peaks in S-phase, and down-regulation of ASPP1 leads to a reduction in DNA synthesis and enhanced senescence in response to drugs that impede DNA replication. These activities of cytoplasmic ASPP1 in opposing p53-mediated p21 expression are in contrast to the role of nuclear ASPP1 in cooperating with p53 to induce the expression of apoptotic target genes, and may help to dampen p53 activity in normal cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Proteína Supressora de Tumor p53
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Senescência Celular
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Reguladoras de Apoptose
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Inibidor de Quinase Dependente de Ciclina p21
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article