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dc.contributor.authorFu, Maofu
dc.contributor.authorWang, Chenguang
dc.contributor.authorWang, Jian
dc.contributor.authorZhang, Xueping
dc.contributor.authorSakamaki, Toshiyuki
dc.contributor.authorYeung, YG
dc.contributor.authorChang, Chawnshang
dc.contributor.authorHopp, Torsten
dc.contributor.authorFuqua, Suzanne A W
dc.contributor.authorJaffray, E
dc.contributor.authorHay, Ronald Thomas
dc.contributor.authorPalvimo, Jorma J
dc.contributor.authorJanne, OA
dc.contributor.authorPestell, RG0
dc.date.accessioned2014-07-04T08:31:01Z
dc.date.available2014-07-04T08:31:01Z
dc.date.issued2002-05
dc.identifier.citationFu , M , Wang , C , Wang , J , Zhang , X , Sakamaki , T , Yeung , YG , Chang , C , Hopp , T , Fuqua , S A W , Jaffray , E , Hay , R T , Palvimo , J J , Janne , OA & Pestell , RG 2002 , ' Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function ' , Molecular and Cellular Biology , vol. 22 , no. 10 , pp. 3373-3388 . https://doi.org/10.1128/MCB.22.10.3373-3388.2002en
dc.identifier.issn0270-7306
dc.identifier.otherPURE: 155778
dc.identifier.otherPURE UUID: 21307110-2c57-45d0-86b0-2a241280827b
dc.identifier.otherWOS: 000175323900016
dc.identifier.otherScopus: 18344371150
dc.identifier.urihttps://hdl.handle.net/10023/4941
dc.descriptionThis work was supported by grants from the NIH (R01CA86072 to R.G.P. and R01CA72038-01 to S.A.W.F.) and The Susan Komen Breast Cancer Foundation (to R.G.P.). R.T.H. and E.J. were supported by the Medical Research Council. Y.-G.Y. is supported by grant CA26504 to E. R. Stanley. Work conducted at the Albert Einstein College of Medicine was supported by Cancer Center Core National Institutes of Health grant 5-P30-CA13330-26.en
dc.description.abstractThe androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both traits repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation. The histone acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK motif. To determine the functional properties governed by AR acetylation, point mutations of the KLKK motif that abrogated acetylation were engineered and examined in vitro and in vivo. The AR acetylation site point mutants showed wild-type trans repression of NF-kappaS, AP-1, and Sp1 activity; wild-type sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational changes. However, acetylation-deficient AR mutants were selectively defective in DHT-induced trans activation of androgen-responsive reporter genes and coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant showed 10-fold increased binding of the N-CoR corepressor compared with the AR wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1) bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival. As AR lysine residue mutations that abrogate acetylation correlate with enhanced binding of the N-CoR repressor in cultured cells, the conserved AR motif may directly or indirectly regulate ligand-dependent corepressor disengagement and, thereby, ligand-dependent trans activation.
dc.format.extent16
dc.language.isoeng
dc.relation.ispartofMolecular and Cellular Biologyen
dc.rightsCopyright © 2002, American Society for Microbiology. All Rights Reserved. Open Access article available from PMCen
dc.subjectProstate-cancer cellsen
dc.subjectAcute promyelocytic leukemiaen
dc.subjectCreb-binding-proteinen
dc.subjectTranscription factor gata-1en
dc.subjectNf-kappa-ben
dc.subjectHistone deacetylaseen
dc.subjectCyclin D1en
dc.subjectEstrogen-receptoren
dc.subjectIn-vivoen
dc.subjectAcetyltransferase activityen
dc.subjectQR Microbiologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQRen
dc.titleAndrogen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression functionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.identifier.doihttps://doi.org/10.1128/MCB.22.10.3373-3388.2002
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC133781/en


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