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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Detalhes bibliográficos
Autores: Sánchez-Molina, Sara, Oliva-Martinez, Jose Luis, Garcia-Vargas, Susana, Valls, Ester, Rojas-Cabañeros, Jose Maria, Martínez-Balbás, Marian A
Formato: artículo
Fecha de publicación:2006
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26127
Acesso em linha:https://hdl.handle.net/20.500.12105/26127
Access Level:acceso abierto
Palavra-chave:Acetylation
cAMP-response-element-binding-protein-binding protein/p300 (CBP/p300)
Histone acetyltransferase activity (HAT activity)
Murine double minute 2 (Mdm2)
NIH 3T3 cell
Ras pathway
Animals
Cell Cycle Proteins
Enzyme Activation
Gene Expression
Histone Acetyltransferases
Mice
NIH 3T3 Cells
Platelet-Derived Growth Factor
Proteasome Endopeptidase Complex
Proto-Oncogene Proteins c-mdm2
Signal Transduction
Transcription Factors
Ubiquitins
Valine
p300-CBP Transcription Factors
ras Proteins
Descrição
Resumo: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.

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