Publication: DNA binding alters ARv7 dimer interactions
dc.contributor.coauthor | Morova, Tunc | |
dc.contributor.coauthor | Geverts, Bart | |
dc.contributor.coauthor | Abraham, Tsion E. | |
dc.contributor.coauthor | Houtsmuller, Adriaan B. | |
dc.contributor.coauthor | van Royen, Martin E. | |
dc.contributor.department | N/A | |
dc.contributor.department | N/A | |
dc.contributor.department | N/A | |
dc.contributor.kuauthor | Özgün, Fatma | |
dc.contributor.kuauthor | Kaya, Zeynep | |
dc.contributor.kuauthor | Lack, Nathan Alan | |
dc.contributor.kuprofile | PhD Student | |
dc.contributor.kuprofile | Master Student | |
dc.contributor.kuprofile | Faculty Member | |
dc.contributor.researchcenter | Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM) | |
dc.contributor.schoolcollegeinstitute | Graduate School of Sciences and Engineering | |
dc.contributor.schoolcollegeinstitute | Graduate School of Sciences and Engineering | |
dc.contributor.schoolcollegeinstitute | School of Medicine | |
dc.contributor.yokid | N/A | |
dc.contributor.yokid | N/A | |
dc.contributor.yokid | 120842 | |
dc.date.accessioned | 2024-11-09T23:53:17Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Androgen 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.indexedby | WoS | |
dc.description.indexedby | Scopus | |
dc.description.indexedby | PubMed | |
dc.description.issue | 14 | |
dc.description.openaccess | NO | |
dc.description.publisherscope | International | |
dc.description.sponsorship | Turkiye Bilimsel ve Teknolojik Arastirma Kurumu [114Z491] This work was supported by the Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (114Z491). | |
dc.description.volume | 134 | |
dc.identifier.doi | 10.1242/jcs.258332 | |
dc.identifier.eissn | 1477-9137 | |
dc.identifier.issn | 0021-9533 | |
dc.identifier.quartile | Q2 | |
dc.identifier.scopus | 2-s2.0-85112424109 | |
dc.identifier.uri | http://dx.doi.org/10.1242/jcs.258332 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14288/14973 | |
dc.identifier.wos | 681395800012 | |
dc.keywords | Androgen receptor | |
dc.keywords | Arv7 | |
dc.keywords | Fluorescence resonance energy transfer | |
dc.keywords | Fluorescence recovery after photobleaching | |
dc.keywords | Confocal microscopy | |
dc.keywords | Prostate cancer | |
dc.keywords | Androgen-deprivation therapy | |
dc.keywords | Receptor splice variants | |
dc.keywords | Prostate-cancer | |
dc.keywords | Structural basis | |
dc.keywords | Resistance | |
dc.keywords | Enzalutamide | |
dc.keywords | Mechanisms | |
dc.keywords | Motifs | |
dc.keywords | Frap | |
dc.language | English | |
dc.publisher | Company Biologists Ltd | |
dc.source | Journal of Cell Science | |
dc.subject | Cell biology | |
dc.subject | Physiology | |
dc.title | DNA binding alters ARv7 dimer interactions | |
dc.type | Journal Article | |
dspace.entity.type | Publication | |
local.contributor.authorid | 0000-0002-2554-7788 | |
local.contributor.authorid | 0000-0002-5626-262X | |
local.contributor.authorid | 0000-0001-7399-5844 | |
local.contributor.kuauthor | Özgün, Fatma | |
local.contributor.kuauthor | Kaya, Zeynep | |
local.contributor.kuauthor | Lack, Nathan Alan |