Adenovirus DNA Binding Protein Interacts with the SNF2-Related CBP Activator Protein (SrCap) and Inhibits SrCap-Mediated Transcription

Xu, Xiequn; Chackalaparampil, Isaac; Monroy, Manuel; Cannella, Maria; Pesek, Elizabeth; Chrivia, John C.; Yaciuk, Peter

doi:10.1128/jvi.75.21.10033-10040.2001

Cited by 10 publications

(8 citation statements)

References 29 publications

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“…Several lines of evidence support the view that SRCAP interacts with CBP (20,48). Here, we show evidence for a SRCAP-CBP interaction on chromosomes, although this interaction could be either direct or indirect.…”

Section: Vol 25 2005 Functional Analysis Of Srcap 6563supporting

confidence: 53%

“…SRCAP was identified as an interactor with the CBP transactivation domain in a yeast two-hybrid protein assay (20), and a monoclonal antibody to SRCAP can pull down CBP from whole-cell lysates (48). Recently, SRCAP was found to be part of a protein complex that shares some subunits with the human NuA4 complex (11), but no CBP was detected in this complex.…”

Section: Resultsmentioning

confidence: 99%

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Human SRCAP and Drosophila melanogaster DOM Are Homologs That Function in the Notch Signaling Pathway

Eissenberg¹,

Wong

Chrivia

2005

Molecular and Cellular Biology

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The putative ATPase chromatin-remodeling machine SRCAP was identified in a yeast two-hybrid protein screen by interaction with the histone acetylase CBP. 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. DOM is the unique SRCAP homolog in Drosophila melanogaster. The goal of this study was to test whether SRCAP is a functional homolog of DOM and to identify potential activities and targets of SRCAP in vivo. We show that human SRCAP complements recessive domino mutant phenotypes. This rescue depends on an intact ATPase homology domain. 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. We show that SRCAP recruits Drosophila CBP to ectopic chromosomal sites, providing the first evidence to suggest that SRCAP and CBP interact directly or indirectly on chromosomes. We show that DOM is a Notch pathway activator in Drosophila and that wild-type SRCAP-but not an ATPase domain mutant-can substitute for DOM in Notch-dependent wing development. We show that SRCAP potentiates Notch-dependent gene activation in HeLa cells. Taken together, these data implicate SRCAP and DOM in developmental gene activation.Most regulated gene expression in eukaryotes is the result of transcriptional regulation. Current models of transcriptional regulation invoke the targeted recruitment of enzymes that make covalent changes in histone and/or DNA structure, in ATPases that remodel histone-DNA interactions, and, in cases of gene activation, in RNA polymerase itself. A major challenge is to identify the diverse roles of chromatin modifiers in transcriptional regulation.SRCAP (SNF2-related CBP-activating protein) shares homology with members of the SNF2/SWI2 class of chromatinremodeling enzymes (20). SRCAP was originally identified in a yeast two-hybrid protein screen for proteins that interact with the histone acetyltransferase CBP (CREB-binding protein). Subsequent studies using transiently transfected reporters have implicated SRCAP as a coactivator for CREB-and nuclear hormone receptor-mediated transcriptional activation (30, 31). The mechanism by which SRCAP activates transcription has not been completely elucidated. Results from a number of studies, including mammalian two-hybrid and coimmunoprecipitation experiments, indicate SRCAP may function in part by recruitment of CBP or other coactivators, such as the arginine methyltransferase CARM-1 and the nuclear hormone receptor coactivator GRIP-1 (20, 31). A role for the conserved ATPase/helicase homology domain in regulation of transcription has not been established, since this activity is dispensable for SRCAP activity in transient transfection assays, nor have the natural chromosomal promoters that utilize SRCAP to regulate transcription been identified.In mammals, the protein most homologous to SRCAP is p400. p400 was ...

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Section: Vol 25 2005 Functional Analysis Of Srcap 6563supporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Human SRCAP and Drosophila melanogaster DOM Are Homologs That Function in the Notch Signaling Pathway

Eissenberg¹,

Wong

Chrivia

2005

Molecular and Cellular Biology

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“…Two of these domains (amino acids 1-1186 and 2316 -2971) do not contain the CBP binding site (located at amino acids 1380 -1670) and therefore may activate transcription through contacts with additional associated proteins. In support of this notion, we have found in immunoprecipitation studies with an anti-SRCAP antibody that SRCAP is part of a large multiprotein complex which, in addition to containing CBP, contains at least 20 other proteins (54).…”

Section: Fig 2 Overexpression Of Srcap Enhances Creb-mediated Transmentioning

confidence: 70%

Regulation of cAMP-responsive Element-binding Protein-mediated Transcription by the SNF2/SWI-related Protein, SRCAP

Monroy¹,

Ruhl²,

Xu³

et al. 2001

Journal of Biological Chemistry

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SRCAP (SNF2-related CPB activator protein) belongs to the SNF2 family of proteins whose members participate in various aspects of transcriptional regulation, including chromatin remodeling. It was identified by its ability to bind to cAMP-responsive-binding protein (CREB)-binding protein (CBP), and it increases the transactivation function of CBP. The phosphoenolpyruvate carboxykinase (PEPCK) promoter was used as a model system to explore the role of SRCAP in the regulation of transcription mediated by factors that utilize CBP as a coactivator. We show that transcription of a PEPCK chloramphenicol acetyltransferase (CAT) reporter gene activated by protein kinase A (PKA) is enhanced 7-fold by SRCAP. In the absence of PKA this SRCAP-mediated enhancement does not occur, suggesting that SRCAP functions as a coactivator for PKA-activated factors such as CREB. Replacing the PEPCK promoter binding site for CREB with a binding site for Gal4 (⌬CRE (cAMP-responsive element) Gal4 PEPCK-CAT reporter gene) blocks the ability of SRCAP to activate transcription despite the presence of PKA. Expression of a Gal-CREB chimera restores the ability of PKA to regulate transcription of the ⌬CRE Gal4 PEPCK gene and restored the ability of SRCAP to stimulate PKAactivated transcription. In addition, SRCAP in the presence of PKA enhances the ability of the Gal-CREB chimera to activate transcription of a Gal-CAT reporter gene that contains only binding sites for Gal4. SRCAP binds to CBP amino acids 280 -460, a region that is important for CBP to function as a coactivator for CREB. Overexpression of a SRCAP peptide corresponding to this CBP binding domain acts as a dominant negative inhibitor of CREB-mediated transcription. Structurefunction studies were done to explore the mechanism(s) by which SRCAP regulates transcription. These studies indicate that the N-terminal region of SRCAP, which contains five of the seven regions that comprise the ATPase domain, is not needed for activation of CREBmediated transcription. SRCAP apparently has several domains that participate in the activation of transcription.The transcription factor cAMP-responsive element-binding protein (CREB) 1 regulates the transcription of a number of genes (for review, see Refs. 1 and 2). It stimulates a low level of basal transcription, which has been proposed to be mediated through action of CREB domains that bind directly to TAF 110, TAF 130, TFIIB and TBP (3-7). CREB also stimulates a much higher level of transcription when it is activated in response to diverse biological stimuli such as neural and hormonal signals. These signals stimulate phosphorylation of CREB within the kinase-inducible domain. Phosphorylation of serine 133 within the kinase-inducible domain by several kinases, including calmodulin kinase II and IV, protein kinase A, ribosomal S6 kinase 1-3, mitogen-and stress-activated protein kinase 1, and mitogen-activated protein kinase-activated protein kinase 2/3, leads to the activation of transcription (for review, see Ref. 8). Although phosphorylation o...

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“…Several of the proteins identified to date as potentially interacting with SRCAPs/Domino/p400 are produced by a virus, presumably to subvert host cell gene expression conducive to the viral life cycle (Johnston et al 1999;Ghosh et al 2000;Xu et al 2001). Interactions between HsSRCAP and glucocorticoid receptor-interacting protein-1 (GRIP-1) as well as co-activator-associated arginine methyltransferase-1 (CARM-1) have been demonstrated .…”

Section: Bioinformatics Analysis Of Proteins Interacting With Tgsrcapmentioning

confidence: 97%

Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening

Nallani

Sullivan

2005

Parasitol Res

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Toxoplasma gondii is an opportunistic protozoan parasite that differentiates into latent cysts (bradyzoite) that can be reactivated during immunosuppression. TgSRCAP (Toxoplasma gondii Snf2-related CBP activator protein) is a SWI2/SNF2 family chromatin remodeler whose expression increases during cyst development. Identifying the proteins associating with TgSRCAP during the pre-cyst stage (tachyzoite) will increase our understanding of how parasite differentiation is initiated. We employed the yeast two-hybrid system to identify proteins that may interact directly with TgSRCAP. A stretch of 1,060 amino acids between ATPase subdomains IV and V of TgSRCAP was chosen as "bait" since the corresponding region in human SRCAP interacts with other proteins, including CREB binding protein. We have identified several novel parasite-specific transcription factors predicted to be in the T. gondii genome. Metabolic enzymes that may participate in cyst development were also identified as interacting with TgSRCAP.

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Adenovirus DNA Binding Protein Interacts with the SNF2-Related CBP Activator Protein (SrCap) and Inhibits SrCap-Mediated Transcription

Cited by 10 publications

References 29 publications

Human SRCAP and Drosophila melanogaster DOM Are Homologs That Function in the Notch Signaling Pathway

Human SRCAP and Drosophila melanogaster DOM Are Homologs That Function in the Notch Signaling Pathway

Regulation of cAMP-responsive Element-binding Protein-mediated Transcription by the SNF2/SWI-related Protein, SRCAP

Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening

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