The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway
Por:
Sánchez-Molina S, Oliva JL, García-Vargas S, Valls E, Rojas JM and Martínez-Balbás MA
Publicada:
1 sep 2006
Resumen:
The CBP [CREB (cAMP-response-element-binding protein)binding protein]/p300 acetyltransferases function as transcriptional co-activators and play critical roles in cell differentiation and proliferation. Accumulating evidence shows that alterations of the CBP/p300 protein levels are linked to human tumours. In the present study, we show that the levels of the CBP/p300 co-activators are decreased dramatically by continuous PDGF (platelet-derived growth factor) and Ras signalling pathway activation in NIH 3T3 fibroblasts. This effect occurs by reducing the expression levels of the CBP/p300 genes. In addition, CBP and p300 are degraded by the 26 S proteasome pathway leading to an overall decrease in the levels of the CBP/p300 proteins. Furthermore, we provide evidence that Mdm2 (murine double minute 2), in the presence of active H-Ras or N-Ras, induces CBP/p300 degradation in NIH 3T3 cells. These findings support a novel mechanism for modulating other signalling transduction pathways that require these common co-activators.
Filiaciones:
Sánchez-Molina S:
Instituto de Biología Molecular de Barcelona, CID, Consejo Superior de Investigaciones Científicas, Parc Cientific de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain
CSIC, Cid, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Biol Celular, Madrid 28220, Spain
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