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

Abstract

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.

Histone-Modifying Complexes Regulate Gene Expression Pertinent to the Differentiation of the Protozoan Parasite Toxoplasma gondii

“…5F). It is tempting to speculate that it interacts with TgSRCAP, a SWI/SNF ATPase noted to increase in expression during bradyzoite differentiation (52) and whose human homologue does interact with CARM1 (43). Finally, it would be of interest to study if TgCARM1 methylates nonhistone substrates as a means of triggering differentiation, as noted in thymocytes (32).…”

NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression

“…The Epstein-Barr virus nuclear protein EBNA3C 507DDDVIEV513 is also critical for SUMO interaction (25). ARIP4 and a closely related SNF-2-domain-containing protein, SRCAP, have similar sequences (15,26), and ARIP4 has now been identified to bind to SUMO-2, with dependence on K33, K35, and K42. These acidic SUMO-interacting amino acids may bind directly to the SUMO lysine-rich repressor patch.…”

Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes

“…It is not immediately apparent why perturbation of a component of a ubiquitously expressed general transcription factor complex may result in a tissue-specific phenotype, such as CdLS. However, we do note that knockdown of TAF6 in Drosophila resulted in a phenotype restricted to the wing area, suggesting a morphogenetic function of TAF6 ing partners, both of which are involved in transcriptional coactivation (46,47); mutations in genes encoding subunits of SWI/ SNF complex, which encompasses the protein product of SRCAP (48), have also been identified in patients with CSS (49). More interestingly, in a recently published study of a cohort of patients with CdLS or CdLS-like phenotypes, de novo mutations in the KBGS-associated gene ANKRD11 were identified, demonstrating the phenotypic overlap between KBGS and CdLS (50).…”