CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.
1997; National Institutes of Health; Volume: 57; Issue: 17 Linguagem: Inglês
Autores
Daniel M. Scolnick, Nabil H. Chehab, Elena S. Stavridi, Marcus Chenchi Lien, Loretta C. Caruso, Elizabeth Morán, Shelley L. Berger, Thanos D. Halazonetis,
Tópico(s)Ubiquitin and proteasome pathways
ResumoThe 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.
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