title: CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, The Wistar Institute, University of Pennsylvania, Philadelphia 19104-4268, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Scolnick
authors.forename: N H
authors.initials: NH
authors.lastname: Chehab
authors.forename: E S
authors.initials: ES
authors.lastname: Stavridi
authors.forename: M C
authors.initials: MC
authors.lastname: Lien
authors.forename: L
authors.initials: L
authors.lastname: Caruso
authors.forename: E
authors.initials: E
authors.lastname: Moran
authors.forename: S L
authors.initials: SL
authors.lastname: Berger
authors.forename: T D
authors.initials: TD
authors.lastname: Halazonetis
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D050882:CREB-Binding Protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human