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Submitted on June 3, 2003
Accepted on September 10, 2003
1 From the Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis MO 63122.; From the Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane Piscataway, NJ 08854
* To whom correspondence should be addressed. E-mail: Chrivia{at}SLU.EDU.
SRCAP (SNF2-related CBP Activator Protein) is a 350 KD protein which shares homology with the SNF2 family of proteins whose members function in various aspects of transcriptional regulation. In various cell types, SRCAP is found in distinct multi-protein complexes which include proteins found in SWI/SNF chromatin remodeling complexes. SRCAP was identified by its ability to bind to CBP and was found to potentiate the ability of CBP to activate transcription. Studies in our laboratory have demonstrated that SRCAP functions as a coactivator for CREB-mediated transcription of a number of promoters, including that of the PEPCK gene. Our current studies demonstrate that SRCAP enhances PEPCK promoter transcription induced by glucocorticoids. SRCAP also enhances GR-mediated transcription of a simple promoter containing only two GRE elements, indicating that SRCAP functions as a GR coactivator. In similar studies SRCAP was also found to serve as a coactivator for the androgen receptor. SRCAP exhibits synergistic activation with nuclear receptor coactivators and functionally interacts in vivo with GRIP-1 and CARM-1. We propose that SRCAP, by virtue of its ability to interact with CBP, functions as a coactivator to regulate transcription initiated by several signaling pathways.
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