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Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators

33 Pages Posted: 4 Apr 2018 Sneak Peek Status: Published

See all articles by Eva De Mol

Eva De Mol

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Elzbieta​ ​ ​Szulc

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Claudio Di Sanza

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Paula Martínez-Cristóbal

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Carlos W. Bertoncini

Republic of Argentina - Instituto​ ​de​ ​Biología​ ​Molecular​ ​y​ ​Celular​ ​de​ ​Rosario​ ​(IBR)

R. Bryn Fenwick

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Marta Frigolé-Vivas

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Marianela Masin

Republic of Argentina - Instituto​ ​de​ ​Biología​ ​Molecular​ ​y​ ​Celular​ ​de​ ​Rosario​ ​(IBR)

Irene Hunter

University of Aberdeen - ​Institute​ ​of​ ​Medical​ ​Sciences

Victor Buzón

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Isabelle Brun-Heath

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Jesús García

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Gianni De Fabritiis

Catalan Institution of Research and Advanced Studies (ICREA)

Eva Estébanez-Perpiñá

Autonomous University of Barcelona - Department of Biochemistry and Molecular Biology

Iain J. McEwan

University of Aberdeen - ​Institute​ ​of​ ​Medical​ ​Sciences

Ángel R. Nebreda

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Xavier Salvatella

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

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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 new molecular insights into the regulation of androgen receptor function and suggest new strategies for treating prostate cancer.

Suggested Citation

De Mol, Eva and ​Szulc, Elzbieta​ ​ and Di Sanza, Claudio and Martínez-Cristóbal, Paula and Bertoncini, Carlos W. and Fenwick, R. Bryn and Frigolé-Vivas, Marta and Masin, Marianela and Hunter, Irene and Buzón, Victor and Brun-Heath, Isabelle and García, Jesús and De Fabritiis, Gianni and Estébanez-Perpiñá, Eva and McEwan, Iain J. and Nebreda, Ángel R. and Salvatella, Xavier, Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators (2018). Available at SSRN: https://ssrn.com/abstract=3155514 or http://dx.doi.org/10.2139/ssrn.3155514
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Eva De Mol

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Elzbieta​ ​ ​Szulc

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Claudio Di Sanza

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Paula Martínez-Cristóbal

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Carlos W. Bertoncini

Republic of Argentina - Instituto​ ​de​ ​Biología​ ​Molecular​ ​y​ ​Celular​ ​de​ ​Rosario​ ​(IBR)

Rosario
Argentina

R. Bryn Fenwick

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Marta Frigolé-Vivas

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Marianela Masin

Republic of Argentina - Instituto​ ​de​ ​Biología​ ​Molecular​ ​y​ ​Celular​ ​de​ ​Rosario​ ​(IBR)

Rosario
Argentina

Irene Hunter

University of Aberdeen - ​Institute​ ​of​ ​Medical​ ​Sciences

​IMS​ ​Building,​ ​Foresterhill
Aberdeen, Scotland AB25​ ​2ZD
United Kingdom

Victor Buzón

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Isabelle Brun-Heath

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Jesús García

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Gianni De Fabritiis

Catalan Institution of Research and Advanced Studies (ICREA)

Passeig Lluís Companys, 23
Barcelona, 08010
Spain

Eva Estébanez-Perpiñá

Autonomous University of Barcelona - Department of Biochemistry and Molecular Biology

Bellaterra
Spain

Iain J. McEwan

University of Aberdeen - ​Institute​ ​of​ ​Medical​ ​Sciences

​IMS​ ​Building,​ ​Foresterhill
Aberdeen, Scotland AB25​ ​2ZD
United Kingdom

Ángel R. Nebreda

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Xavier Salvatella (Contact Author)

Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona) ( email )

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

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