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

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...

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Published in:Biochemical journal 2006-09, Vol.398 (2), p.215-224
Main Authors: Sánchez-Molina, Sara, Oliva, José Luis, García-Vargas, Susana, Valls, Ester, Rojas, José M, Martínez-Balbás, Marian A
Format: Article
Language:English
Subjects:
Animals
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Enzyme Activation - drug effects
Gene Expression
Histone Acetyltransferases - genetics
Histone Acetyltransferases - metabolism
Mice
NIH 3T3 Cells
p300-CBP Transcription Factors
Platelet-Derived Growth Factor - pharmacology
Proteasome Endopeptidase Complex - metabolism
Proto-Oncogene Proteins c-mdm2 - genetics
Proto-Oncogene Proteins c-mdm2 - metabolism
ras Proteins - genetics
ras Proteins - metabolism
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
Ubiquitin - metabolism
Valine - genetics
Valine - metabolism
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Summary: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.
ISSN:0264-6021
1470-8728
1470-8728
DOI:10.1042/BJ20060052