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SNF2-Related CBP Activator Protein (SRCAP) Functions as a Coactivator of Steroid Receptor-Mediated Transcription through Synergistic Interactions with CARM-1 and GRIP-1

Department of Pharmacological and Physiological Science (M.A.M., N.M.S., L.C., M.R., J.C.C.), St. Louis University School of Medicine, St. Louis, Missouri 63104; and the Department of Pharmacology (J.D.C.), University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Address all correspondence and requests for reprints to: John C. Chrivia, Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri 63122. E-mail: Chrivia{at}slu.edu.

SRCAP (SNF2-related CBP activator protein) is a 350-kDa protein that 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 multiprotein complexes that 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 phosphoenolpyruvate carboxykinase gene. Our current studies demonstrate that SRCAP enhances phosphoenolpyruvate carboxykinase promoter transcription induced by glucocorticoids. SRCAP also enhances glucocorticoid receptor-mediated transcription of a simple promoter containing only two glucocorticoid response elements, indicating that SRCAP functions as a glucocorticoid receptor 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 glucocorticoid receptor-interacting protein-1 and coactivator-associated arginine methyltransferase-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.

NURSA Molecule Pages Link:

Nuclear Receptors:   GR  |  AR

Coregulators:   CARM1  |  CBP  |  GRIP1

Ligands:   Dexamethasone  |  Dihydrotestosterone  |  RU486

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