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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.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.issn 0969-2126
dc.identifier.uri http://hdl.handle.net/10230/37181
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.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Structure. 2018;26(1):145-52
dc.rights © Elsevier http://dx.doi.org/10.1016/j.str.2017.11.007
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.identifier.doi http://dx.doi.org/10.1016/j.str.2017.11.007
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.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.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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