Nature 374, 85 - 88 (02 March 2002); doi:10.1038/374085a0

Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP

James R. Lundblad, Roland P. S. Kwok, Megan E. Laurance, Marian L. Harter^* & Richard H. Goodman^†

Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA
^* Department of Molecular Biology, Cleveland Clinic Research Institute, Cleveland, Ohio 44195, USA
^† To whom correspondence should be addressed

THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB¹. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.

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