CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.
The structurally related transcriptional coactivators p300 and CBP possess histone acetyltransferase activity and associate with P/CAF, which is also a histone acetyltransferase. CBP and p300 have properties of tumor suppressor proteins; their interaction with P/CAF is disrupted by the adenoviral E1A oncoprotein, and the genes encoding CBP and p300 are ... mutated in human cancer. We observed a physical interaction between the transactivation domain of the p53 tumor suppressor protein and CBP. Furthermore, CBP and P/CAF enhanced the ability of p53 to activate expression of the endogenous p21(cip1/waf1) gene, whereas E1A and dominant negative CBP mutants suppressed p53-dependent p21(cip1/waf1) expression. These studies link two tumor suppressor families and provide a framework for understanding the molecular mechanism by which p53 activates transcription.
Mesh Terms:
Binding Sites, Breast Neoplasms, CREB-Binding Protein, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, Humans, Nuclear Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Binding Sites, Breast Neoplasms, CREB-Binding Protein, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, Humans, Nuclear Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Cancer Res.
Date: Sep. 01, 1997
PubMed ID: 9288775
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