Publication:
DNA binding alters ARv7 dimer interactions

dc.contributor.coauthorMorova, Tunc
dc.contributor.coauthorGeverts, Bart
dc.contributor.coauthorAbraham, Tsion E.
dc.contributor.coauthorHoutsmuller, Adriaan B.
dc.contributor.coauthorvan Royen, Martin E.
dc.contributor.departmentN/A
dc.contributor.departmentN/A
dc.contributor.departmentN/A
dc.contributor.kuauthorÖzgün, Fatma
dc.contributor.kuauthorKaya, Zeynep
dc.contributor.kuauthorLack, Nathan Alan
dc.contributor.kuprofilePhD Student
dc.contributor.kuprofileMaster Student
dc.contributor.kuprofileFaculty Member
dc.contributor.researchcenterKoç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
dc.contributor.schoolcollegeinstituteGraduate School of Sciences and Engineering
dc.contributor.schoolcollegeinstituteGraduate School of Sciences and Engineering
dc.contributor.schoolcollegeinstituteSchool of Medicine
dc.contributor.yokidN/A
dc.contributor.yokidN/A
dc.contributor.yokid120842
dc.date.accessioned2024-11-09T23:53:17Z
dc.date.issued2021
dc.description.abstractAndrogen receptor (AR) splice variants are proposed to be a potential driver of lethal castration-resistant prostate cancer. AR splice variant 7 (ARv7) is the most commonly observed isoform and strongly correlates with resistance to second-generation anti-androgens. Despite this clinical evidence, the interplay between ARv7 and the highly expressed full-length AR (ARfl) remains unclear. In this work, we show that ARfl/ARv7 heterodimers readily form in the nucleus via an intermolecular N/C interaction that brings the four termini of the proteins in close proximity. Combining fluorescence resonance energy transfer and fluorescence recovery after photobleaching, we demonstrate that these heterodimers undergo conformational changes following DNA binding, indicating dynamic nuclear receptor interaction. Although transcriptionally active, ARv7 can only form short-term interactions with DNA at highly accessible high-occupancy ARfl binding sites. Dimerization with ARfl does not affect ARv7 binding dynamics, suggesting that DNA binding occupancy is determined by the individual protein monomers and not the homodimer or heterodimer complex. Overall, these biophysical studies reveal detailed properties of ARv7 dynamics as both a homodimer or heterodimer with ARfl.
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue14
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsorshipTurkiye Bilimsel ve Teknolojik Arastirma Kurumu [114Z491] This work was supported by the Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (114Z491).
dc.description.volume134
dc.identifier.doi10.1242/jcs.258332
dc.identifier.eissn1477-9137
dc.identifier.issn0021-9533
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-85112424109
dc.identifier.urihttp://dx.doi.org/10.1242/jcs.258332
dc.identifier.urihttps://hdl.handle.net/20.500.14288/14973
dc.identifier.wos681395800012
dc.keywordsAndrogen receptor
dc.keywordsArv7
dc.keywordsFluorescence resonance energy transfer
dc.keywordsFluorescence recovery after photobleaching
dc.keywordsConfocal microscopy
dc.keywordsProstate cancer
dc.keywordsAndrogen-deprivation therapy
dc.keywordsReceptor splice variants
dc.keywordsProstate-cancer
dc.keywordsStructural basis
dc.keywordsResistance
dc.keywordsEnzalutamide
dc.keywordsMechanisms
dc.keywordsMotifs
dc.keywordsFrap
dc.languageEnglish
dc.publisherCompany Biologists Ltd
dc.sourceJournal of Cell Science
dc.subjectCell biology
dc.subjectPhysiology
dc.titleDNA binding alters ARv7 dimer interactions
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.authorid0000-0002-2554-7788
local.contributor.authorid0000-0002-5626-262X
local.contributor.authorid0000-0001-7399-5844
local.contributor.kuauthorÖzgün, Fatma
local.contributor.kuauthorKaya, Zeynep
local.contributor.kuauthorLack, Nathan Alan

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