Disease relevance of SRCAP

• Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP [1].
• These data suggest a novel mechanism of adenovirus host cell control by which DBP binds to and inactivates SrCap, a member of the SNF2 chromatin-remodeling protein family [2].

High impact information on SRCAP

• GAS41 is a common subunit of the TIP60 and SRCAP complexes and is essential for cell growth and viability [3].
• DOM is the unique SRCAP homolog in Drosophila melanogaster [4].
• SRCAP is implicated in the transcriptional coactivation of cyclic AMP- and steroid-dependent promoters, but no natural chromosomal targets for SRCAP regulation have been identified [4].
• Taken together, these data implicate SRCAP and DOM in developmental gene activation [4].
• We show that SRCAP potentiates Notch-dependent gene activation in HeLa cells [4].

Biological context of SRCAP

• Transfection experiments demonstrate that SRCAP is able to activate transcription when expressed as a Gal-SRCAP chimera and that SRCAP also enhances the ability of CBP to activate transcription [5].
• In various cell types, SRCAP is found in distinct multiprotein complexes that include proteins found in SWI/SNF chromatin remodeling complexes [6].
• We show that human SRCAP complements recessive domino mutant phenotypes [4].
• SRCAP colocalizes extensively with DOM on Drosophila polytene chromosomes and is recruited to sites of active transcription, such as steroid-regulated loci, but not to activated heat shock loci [4].
• However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP [1].

Associations of SRCAP with chemical compounds

• Our current studies demonstrate that SRCAP enhances phosphoenolpyruvate carboxykinase promoter transcription induced by glucocorticoids [6].
• The highest levels of SRCAP were observed on the active SP-1, G3BP, and FAD synthetase promoters [7].

Physical interactions of SRCAP

• SRCAP was identified by its ability to bind to CBP and was found to potentiate the ability of CBP to activate transcription [6].
• We have previously demonstrated that the Adenovirus 2 DNA Binding Protein (DBP) binds to SrCap and inhibits the transcription mediated by the carboxyl-terminal region of SrCap (amino acids 1275-2971) [8].

Enzymatic interactions of SRCAP

• Mechanistic studies revealed that the human INO80 complex catalyzes nucleosome sliding and the SRCAP complex catalyzes ATP-dependent exchange of histone H2A/H2B dimers containing the histone variant H2A.Z into nucleosomes [9].

Regulatory relationships of SRCAP

• Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription [8].
• In addition, DBP also inhibits the ability of SrCap to enhance Protein Kinase A (PKA) activated transcription of the enkaphalin promoter [8].

Other interactions of SRCAP

• 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 [6].
• In similar studies, SRCAP was also found to serve as a coactivator for the androgen receptor [6].
• 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 [6].
• We also found that DBP has no effect on transcription mediated by a transcriptional activator that is not related to SrCap, indicating that our reported transcriptional inhibition is specific for SrCap and not due to nonspecific effects of DBP's DNA binding activity on the CAT reporter plasmid [8].

Analytical, diagnostic and therapeutic context of SRCAP

• Molecular cloning and characterization of an SRCAP chromatin remodeling homologue in Toxoplasma gondii [10].

References