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

被引：33

作者：

De Mol, Eva ^{[1
]}

Szulc, Elzbieta ^{[1
]}

Di Sanza, Claudio ^{[1
]}

Martinez-Cristobal, Paula ^{[1
]}

Bertoncini, Carlos W. ^{[1
,7
]}

Bryn Fenwick, R. ^{[1
,8
,9
]}

Frigole-Vivas, Marta ^{[1
]}

Masin, Marianela ^{[1
,7
]}

Hunter, Irene ^{[2
]}

Buzon, Victor ^{[1
]}

Brun-Heath, Isabelle ^{[1
]}

Garcia, Jesus ^{[1
]}

De Fabritiis, Gianni ^{[3
,4
]}

Estebanez-Perpina, Eva ^{[5
,6
]}

McEwan, Iain J. ^{[2
]}

Nebreda, Angel R. ^{[1
,4
]}

Salvatella, Xavier ^{[1
,4
]}

机构：

[1] Barcelona Inst Sci & Technol, IRB Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain

[2] Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, IMS Bldg,Foresterhill, Aberdeen AB25 2ZD, Scotland

[3] Univ Pompeu Fabra, Computat Biophys Lab GRIB IMIM, Barcelona Biomed Res Pk PRBB,Doctor Aiguader 88, Barcelona 08003, Spain

[4] ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain

[5] Univ Barcelona, Dept Bioquim & Biomed Mol, Baldiri Reixac 15-21, E-08028 Barcelona, Spain

[6] Univ Barcelona IBUB, Inst Biomed, Baldiri Reixac 15-21, Barcelona 08028, Spain

[7] Consejo Nacl Invest Cient & Tecn, Inst Biol Mol & Cellular Rosario IBR, Rosario, Santa Fe, Argentina

[8] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

STRUCTURE | 2018年 / 26卷 / 01期

基金：

欧洲研究理事会;

关键词：

CARBOXYL-TERMINAL DOMAIN; RNA-POLYMERASE-II; ADVANCED PROSTATE-CANCER; INDUCED ALPHA-HELIX; PHOSPHATASE FCP1; FACTOR-TFIIF; ACTIVATION DOMAINS; STRUCTURAL BASIS; NMR STRUCTURE; BINDING;

D O I：

10.1016/j.str.2017.11.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：145 / +

页数：11

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