2024-03-28T16:51:31Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1217842021-11-22T12:51:12Zcom_10261_41com_10261_1com_10261_76com_10261_5col_10261_294col_10261_329
The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway
Sánchez-Molina, Sara
Oliva, José Luis
García-Vargas, Susana
Valls, Ester
Rojas, José María
Martínez-Balbás, Marian
Ministerio de Educación y Ciencia (España)
Generalitat de Catalunya
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. © 2006 Biochemical Society.
This work was supported by grants to M. A. M.-B. from the Ministerio de Educación y Ciencia (SAF2002-00741 and PAMNBMB) and to J. M. R. (SAF2003-02604). S. S.-M. is the recipient of a fellowship from the Generalitat de Catalunya
Peer Reviewed
2015-09-08T10:36:41Z
2015-09-08T10:36:41Z
2006-05-17
2015-09-08T10:36:41Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1042/BJ20060052
issn: 0264-6021
Biochemical Journal 398(2): 215-224 (2006)
http://hdl.handle.net/10261/121784
10.1042/BJ20060052
http://dx.doi.org/10.13039/501100002809
16704373
http://dx.doi.org/10.1042/BJ20060052
Sí
none
Portland Press