Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation

Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This r...

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Detalles Bibliográficos
Autores principales: Valls, Ester, Blanco-García, Noemí, Aquizu, Naiara, Piedra, David, Estarás, Conchi, de la Cruz, Xavier, Martínez-Balbás, Marian A.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2007
Materias:
Molecular Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874590/
https://www.ncbi.nlm.nih.gov/pubmed/17341466
http://dx.doi.org/10.1093/nar/gkl1113
Descripción
Sumario:Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb-independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins.

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