Sánchez-Molina, SaraOliva-Martinez, Jose LuisGarcia-Vargas, SusanaValls, EsterRojas-Cabañeros, Jose MariaMartínez-Balbás, Marian A2025-01-242025-01-242006-09-01Sánchez-Molina S, Oliva JL, García-Vargas S, Valls E, Rojas JM, Martínez-Balbás MA. The histone acetyltransferases CBP/p300 are degraded in NIH 3T3 cells by activation of Ras signalling pathway. Biochem J. 2006 Sep 1;398(2):215-24.0264-6021https://pmc.ncbi.nlm.nih.gov/articles/PMC1550303/https://hdl.handle.net/20.500.12105/26127The 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AcetylationcAMP-response-element-binding-protein-binding protein/p300 (CBP/p300)Histone acetyltransferase activity (HAT activity)Murine double minute 2 (Mdm2)NIH 3T3 cellRas pathwayAnimalsCell Cycle ProteinsEnzyme ActivationGene ExpressionHistone AcetyltransferasesMiceNIH 3T3 CellsPlatelet-Derived Growth FactorProteasome Endopeptidase ComplexProto-Oncogene Proteins c-mdm2Signal TransductionTranscription FactorsUbiquitinsValinep300-CBP Transcription Factorsras ProteinsAttribution-NonCommercial-NoDerivatives 4.0 International167043733982215-2410.1042/BJ200600521470-8728The Biochemical journalopen access