Researcher:
Kaya, Zeynep

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Master Student

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Zeynep

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Kaya

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Kaya, Zeynep

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2017 - 201912020 - 20211

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Researcher Of Publications: search.filters.isAuthorOfPublication.1b4943d1-b399-4360-b31f-fcd43f6bf6fe

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    DNA binding alters ARv7 dimer interactions
    (Company Biologists Ltd, 2021) Morova, Tunc; Geverts, Bart; Abraham, Tsion E.; Houtsmuller, Adriaan B.; van Royen, Martin E.; N/A; N/A; N/A; Özgün, Fatma; Kaya, Zeynep; Lack, Nathan Alan; PhD Student; Master Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; School of Medicine; N/A; N/A; 120842
    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.
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    PublicationOpen Access
    Kdm2b, an h3k36-specific demethylase, regulates apoptotic response of gbm cells to trail
    (Nature Publishing Group (NPG), 2017) Gumus, Zeynep H.; Kurt, İbrahim Çağrı; Sur, İlknur Erdem; Kaya, Ezgi; Cingöz, Ahmet; Kazancıoğlu, Selena; Kahya, Zeynep; Toparlak, Ömer Duhan; Şenbabaoğlu, Filiz; Kaya, Zeynep; Özyerli, Ezgi; Karahüseyinoğlu, Serçin; Lack, Nathan Alan; Önder, Tamer Tevfik; Önder, Tuğba Bağcı; PhD Student; Undergraduate Student; Other; PhD Student; Faculty Member; Faculty Member; Faculty Member; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 110772; 120842; 42946; 184359
    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill tumor cells. TRAIL resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at the epigenetic level is not understood. In this study, we investigated novel epigenetic mechanisms regulating TRAIL response in glioblastoma multiforme (GBM) cells by a short-hairpin RNA loss-of-function screen. We interrogated 48 genes in DNA and histone modification pathways and identified KDM2B, an H3K36-specific demethylase, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity, the activation of caspase-8, -3 and -7 and PARP cleavage. KDM2B knockdown also accelerated the apoptosis, as revealed by live-cell imaging experiments. To decipher the downstream molecular pathways regulated by KDM2B, levels of apoptosis-related genes were examined by RNA-sequencing upon KDM2B loss, which revealed derepression of proapoptotic genes Harakiri (HRK), caspase-7 and death receptor 4 (DR4) and repression of antiapoptotic genes. The apoptosis phenotype was partly dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. KDM2B-silenced tumors exhibited slower growth in vivo. Taken together, our findings suggest a novel mechanism, where the key apoptosis components are under epigenetic control of KDM2B in GBM cells.