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PubMed · 10097092

Factor-specific modulation of CREB-binding protein acetyltransferase activity.

V Perissi·J S Dasen·R Kurokawa·Z Wang·E Korzus·D W Rose·C K Glass·M G Rosenfeld
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Abstract

CREB-binding proteins (CBP) and p300 are essential transcriptional coactivators for a large number of regulated DNA-binding transcription factors, including CREB, nuclear receptors, and STATs. CBP and p300 function in part by mediating the assembly of multiprotein complexes that contain additional cofactors such as p300/CBP interacting protein (p/CIP), a member of the p160/SRC family of coactivators, and the p300/CBP associated factor p/CAF. In addition to serving as molecular scaffolds, CBP and p300 each possess intrinsic acetyltransferase activities that are required for their function as coactivators. Here we report that the adenovirus E1A protein inhibits the acetyltransferase activity of CBP on binding to the C/H3 domain, whereas binding of CREB, or a CREB/E1A fusion protein to the KIX domain, fails to inhibit CBP acetyltransferase activity. Surprisingly, p/CIP can either inhibit or stimulate CBP acetyltransferase activity depending on the specific substrate evaluated and the functional domains present in the p/CIP protein. While the CBP interaction domain of p/CIP inhibits acetylation of histones H3, H4, or high mobility group by CBP, it enhances acetylation of other substrates, such as Pit-1. These observations suggest that the acetyltransferase activities of CBP/p300 and p/CAF can be differentially modulated by factors binding to distinct regions of CBP/p300. Because these interactions are likely to result in differential effects on the coactivator functions of CBP/p300 for different classes of transcription factors, regulation of CBP/p300 acetyltransferase activity may represent a mechanism for integration of diverse signaling pathways.

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AcetylationAcetyltransferasesAdenovirus E1A ProteinsAnimalsBinding SitesCREB-Binding ProteinCell LineCyclic AMP Response Element-Binding ProteinFibroblastsHistonesKineticsNuclear ProteinsRatsRecombinant Fusion ProteinsRecombinant ProteinsSubstrate SpecificityTrans-ActivatorsTransfectionJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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V Perissi, J S Dasen, R Kurokawa, Z Wang, E Korzus, D W Rose, C K Glass, M G Rosenfeld. 1999-03-30. Factor-specific modulation of CREB-binding protein acetyltransferase activity.. https://doi.org/10.1073/pnas.96.7.3652

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