Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators

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• dc.contributor.author De Mol, Eva
• dc.contributor.author Szulc, Elzbieta
• dc.contributor.author Di Sanza, Claudio
• dc.contributor.author Martínez-Cristóbal, Paula
• dc.contributor.author Bertoncini, Carlos W.
• dc.contributor.author Fenwick, R. Bryn
• dc.contributor.author Frigolé-Vivas, Marta
• dc.contributor.author Masín, Marianela
• dc.contributor.author Hunter, Irene
• dc.contributor.author Buzón, Víctor
• dc.contributor.author Brun-Heath, Isabelle
• dc.contributor.author García, Jesús
• dc.contributor.author De Fabritiis, Gianni
• dc.contributor.author Estébanez-Perpiñá, Eva
• dc.contributor.author McEwan, Iain J.
• dc.contributor.author Nebreda, Ángel R.
• dc.contributor.author Salvatella, Xavier
• dc.date.accessioned 2019-05-07T08:01:52Z
• dc.date.available 2019-05-07T08:01:52Z
• dc.date.issued 2018
• dc.description.abstract The androgen receptor is a transcription factor that plays a key role in the development of prostate cancer, and its interactions with general transcription regulators are therefore of potential therapeutic interest. The mechanistic basis of these interactions is poorly understood due to the intrinsically disordered nature of the transactivation domain of the androgen receptor and the generally transient nature of the protein-protein interactions that trigger transcription. Here, we identify a motif of the transactivation domain that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. These findings provide molecular insights into the regulation of androgen receptor function and suggest strategies for treating castration-resistant prostate cancer.
• dc.description.sponsorship This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (E.D.M., E.S., and X.S.), MINECO (BIO2012-31043 and BIO2015-70092-R to X.S., BIO2014-53095-P to G.D.F.), Marató de TV3 (102030 to X.S. and 102031 to E.E.-P), the COFUND program of the European Commission (C.D.S.), the European Research Council (CONCERT, contract number 648201 to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.), the Serra Hunter Program (E.E.-P.), AGAUR (SGR-2014-56RR14 to E.E.-P), and FEDER (G.D.F.). I.H. was supported by funding from the Chief Scientist's Office of the Scottish Government (ETM-258, ETM-382). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain).
• dc.format.mimetype application/pdf
• dc.identifier.citation De Mol E, Szulc E, Di Sanza C, Martínez-Cristóbal P, Bertoncini CW, Fenwick RB et al. Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators. Structure. 2018;26(1):145-52. DOI: 10.1016/j.str.2017.11.007
• dc.identifier.doi http://dx.doi.org/10.1016/j.str.2017.11.007
• dc.identifier.issn 0969-2126
• dc.identifier.uri http://hdl.handle.net/10230/37181
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Structure. 2018;26(1):145-52
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2012-31043
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-70092-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-53095-P
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.str.2017.11.007
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Androgen receptor
• dc.subject.keyword Castration-resistant prostate cancer
• dc.subject.keyword Intrinsic disorder
• dc.subject.keyword Protein phosphorylation
• dc.subject.keyword Protein-protein interactions
• dc.subject.keyword Transcription
• dc.subject.keyword Transcription factor IIF
• dc.title Regulation of androgen receptor activity by transient interactions of its transactivation domain with general transcription regulators
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion