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.
Scolnick
D M
DM
Department of Molecular Genetics, The Wistar Institute, University of Pennsylvania, Philadelphia 19104-4268, USA.
Chehab
N H
NH
Stavridi
E S
ES
Lien
M C
MC
Caruso
L
L
Moran
E
E
Berger
S L
SL
Halazonetis
T D
TD
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*
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