The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway

Sara Sánchez-Molina , José L Oliva , Susana García-Vargas , Ester Valls , José M Rojas , Marian A Martínez-Balbás , Marian A Martínez-Balbás (1)

1 Institut de Biologia Molecular de Barcelona

The CBP and p300 (CBP/p300) acetyltransferases function as transcriptional co-activators and play critical roles in cell differentiation and proliferation. Accumulating evidence shows that alterations of the p300 and CBP (CBP/p300) protein levels are linked to human tumors. In the present study, we show that the levels of the CBP and p300 co-activators decrease dramatically by continuous PDGF and Ras signaling pathway activation in NIH 3T3 fibroblasts. This effect occurs by reducing the expression levels of the CBP and p300 genes. In addition, CBP and p300 are degraded by the 26S proteasome pathway leading to an overall decrease in the levels of the CBP and p300 proteins. Furthermore, we provide evidence that Mdm2, in the presence of active H-Ras or N-Ras induces CBP/p300 degradation in NIH3T3 cells. These findings support a novel mechanism for modulating other signaling transduction pathways that require these common co-activators.

Mots clés: Life Sciences

Sara Sánchez-Molina, José L Oliva, Susana García-Vargas, Ester Valls, José M Rojas, et al.. The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway. Biochemical Journal, 2006, 398 (2), pp.215-224. ⟨10.1042/BJ20060052⟩. ⟨hal-00478509⟩