ETS-domain transcription factor Elk-1 mediates neuronal survival: SMN as a potential target

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dc.authorid0000-0003-0352-1947
dc.contributor.authorDemir, Özlem
dc.contributor.authorAysit, Neşe
dc.contributor.authorÖnder, Zeynep
dc.contributor.authorTürkel, Nezaket
dc.contributor.authorÖztürk, Gürkan
dc.contributor.authorSharrocks, Andrew D.
dc.contributor.authorAksan Kurnaz, Işıl
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:35:38Z
dc.date.available10.07.201910:49:14
dc.date.available2019-07-10T19:35:38Z
dc.date.issued2011
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractElk-1 belongs to the ternary complex factors (TCFs) subfamily of the ETS domain proteins, and plays a critical role in the expression of immediate-early genes (IEGs) upon mitogen stimulation and activation of the mitogen-activated protein kinase (MAPK) cascade. The association of TCFs with serum response elements (SREs) on IEG promoters has been widely studied and a role for Elk-1 in promoting cell cycle entry has been determined. However, the presence of the ETS domain transcription factor Elk-1 in axons and dendrites of post-mitotic adult brain neurons has implications for an alternative function for Elk-1 in neurons other than controlling proliferation. In this study, possible alternative roles for Elk-1 in neurons were investigated, and it was demonstrated that blocking TCF-mediated transactivation in neuronal cells leads to apoptosis through a caspase-dependent mechanism. Indeed RNAi-mediated depletion of endogenous Elk-1 results in increased caspase activity. Conversely, overexpression of either Elk-1 or Elk-VP16 fusion proteins was shown to rescue PC12 cells from chemically-induced apoptosis, and that higher levels of endogenous Elk-1 correlated with longer survival of DRGs in culture. It was shown that Elk-1 regulated the Mcl-1 gene expression required for survival, and that RNAi-mediated degradation of endogenous Elk-1 resulted in elimination of the mcl-1 message. We have further identified the survival-of-motor neuron-1 (SMN1) gene as a novel target of Elk-1, and show that the ets motifs in the SMN1 promoter are involved in this regulation.
dc.description.sponsorship106S247 Australian Diabetes Society Wellcome Trusten_US
dc.description.sponsorshipWellcome Trusten_US
dc.description.sponsorshipRoyal Society of Londonen_US
dc.identifier.citationDemir, Ö., Aysit, N., Önder, Z., Türkel, N., Öztürk, G., Sharrocks, A. D. ... Aksan Kurnaz, I. (2011). ETS-domain transcription factor Elk-1 mediates neuronal survival: SMN as a potential target. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1812(6), 652-662. https://dx.doi.org/10.1016/j.bbadis.2011.02.012
dc.identifier.doi10.1016/j.bbadis.2011.02.012
dc.identifier.endpage662
dc.identifier.issn0925-4439
dc.identifier.issue6
dc.identifier.scopusqualityQ1
dc.identifier.startpage652
dc.identifier.urihttps://hdl.handle.net/20.500.12511/878
dc.identifier.urihttps://dx.doi.org/10.1016/j.bbadis.2011.02.012
dc.identifier.volume1812
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofBiochimica et Biophysica Acta - Molecular Basis of Diseaseen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/106S247
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNeuronal Apoptosis
dc.subjectNeuroprotection
dc.subjectSMA
dc.subjectSMN
dc.subjectSurvival
dc.subjectTranscription Factor
dc.titleETS-domain transcription factor Elk-1 mediates neuronal survival: SMN as a potential target
dc.typeArticle

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