Identification of transcriptional and phosphatase regulators as interaction partners of human ADA3, a component of histone acetyltransferase complexes

dc.contributor.authorZencir, Sevil
dc.contributor.authorSike, Adam
dc.contributor.authorDobson, Melanie J.
dc.contributor.authorAyaydin, Ferhan
dc.contributor.authorBoros, Imre
dc.contributor.authorTopcu, Zeki
dc.date.accessioned2019-10-27T21:52:53Z
dc.date.available2019-10-27T21:52:53Z
dc.date.issued2013
dc.departmentEge Üniversitesien_US
dc.description.abstractADA (alteration/deficiency in activation) 3 is a conserved component of several transcriptional adaptor and HAT (histone acetyltransferase) complexes that regulate RNA polymerase II-mediated gene expression. Within the HAT complexes ADA3 is associated with ADA2 and the HAT GCN5 (general control non-repressed 5). ADA3 plays roles in diverse cellular processes and also in malignancies by modulating GCN5 catalytic activity and/or by interactions with other regulators. To gain a better understanding of ADA3 function, we used a yeast two-hybrid approach to screen a human fetal cDNA library for proteins that interacted with hADA3 (human ADA3). We identified three novel hADA3-interacting partners, a transcriptional regulator, AATF (apoptosis-antagonizing transcription factor), and regulatory subunits of the PP1 (protein phosphatase 1) and PP2A (protein phosphatase 2A) [PPP1R7 (PP1 regulatory subunit 7) and PPP2R5D (PP2A 56 kDa regulatory subunit 8 isoform) respectively]. Analysis of truncated versions of hADA3 indicated that the C-terminal ADA2-interacting domain was not required for these interactions. Fluorescent microscopy analysis and co-immunoprecipitation provided support for the co-localization and interaction of hADA3 with these proteins in human cells. Expression of the interacting proteins altered expression of an hADA3-regulated reporter gene, suggesting functional consequences for the interactions. The detected interactions of hADA3 might extend the spectrum of mechanisms by which ADA3 can contribute to the regulation of gene expression and shed light on processes mediated by these newly identified ADA3 partners.en_US
dc.description.sponsorshipTUBITAK (Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108T945]; NSERC (Natural Sciences and Engineering Research Council of Canada)Natural Sciences and Engineering Research Council of Canada [155268]; European Union via the European Social Fund; Tarsadalmi Megujulas Operative Program [TAMOP-4.2.2/B-10/1-2010-0012, TAMOP-4.2.1./B-09/1/KONV-2010-0005]; Hungarian State Science Fund; Turkish Hungarian Bilateral ProjectTurkiye Cumhuriyeti Kalkinma Bakanligien_US
dc.description.sponsorshipThis work was supported by the TUBITAK (Scientific and Technological Research Council of Turkey) [grant number 108T945 (to Z.T.)], the NSERC (Natural Sciences and Engineering Research Council of Canada) [grant number 155268 (to M.J.D.)], the European Union via the European Social Fund, the Tarsadalmi Megujulas Operative Program (project numbers TAMOP-4.2.2/B-10/1-2010-0012 and TAMOP-4.2.1./B-09/1/KONV-2010-0005) the Hungarian State Science Fund and the Turkish Hungarian Bilateral Project.en_US
dc.identifier.doi10.1042/BJ20120452en_US
dc.identifier.endpage320en_US
dc.identifier.issn0264-6021
dc.identifier.pmid23167988en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage311en_US
dc.identifier.urihttps://doi.org/10.1042/BJ20120452
dc.identifier.urihttps://hdl.handle.net/11454/47762
dc.identifier.volume450en_US
dc.identifier.wosWOS:000315253300007en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPortland Press Ltden_US
dc.relation.ispartofBiochemical Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectalteration/deficiency in activation 3 (ADA3)en_US
dc.subjecthistone acetyltransferaseen_US
dc.subjectprotein-protein interactionen_US
dc.subjecttranscriptional regulationen_US
dc.subjectyeast two-hybrid technologyen_US
dc.subjectSpt/Ada/Gcn5/acetyltransferase (SAGA)en_US
dc.titleIdentification of transcriptional and phosphatase regulators as interaction partners of human ADA3, a component of histone acetyltransferase complexesen_US
dc.typeArticleen_US

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