Interaction and functional cooperation of the cancer-amplified transcriptional coactivator activating signal cointegrator-2 and E2F-1 in cell proliferation.
Mol Cancer Res
; 1(13): 948-58, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14638867
ABSTRACT
Activating signal cointegrator-2 (ASC-2), a novel coactivator, is amplified in several cancer cells and known to interact with mitogenic transcription factors, including serum response factor, activating protein-1, and nuclear factor-kappaB, suggesting the physiological role of ASC-2 in the promotion of cell proliferation. Here, we show that the expression pattern of ASC-2 was correlated with that of E2F-1 for protein increases at G(1) and S phase. Furthermore, cells stably overexpressing ASC-2 had an increased cell proliferation profile. These results prompted us to examine the functional interaction of ASC-2 and E2F-1. Biochemical evidence of protein interaction indicated that the transactivation domain of E2F-1 interacted with the COOH-terminal region of ASC-2. The importance of the E2F-1-ASC-2 interaction was supported by the demonstration that the coexpression of ASC-2 and E2F-1 synergistically transactivated E2F-1-driven gene transcription and the acetylation of E2F-1 protein was necessary for ASC-2-mediated transcriptional coactivation. Interestingly, overexpression of ASC-2 increased the endogenous protein level of E2F-1 in cells, resulting from the prolonged protein stability of E2F-1. Taken together, these results suggest that the cancer-amplified transcriptional coactivator ASC-2 may promote cell proliferation through enhancement of E2F-1-dependent transactivation of the expression of genes associated with cell cycle progression that may be available to favor tumor growth in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Transporte
/
Transativadores
/
Proteínas de Ciclo Celular
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos