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

Structure (London, England : 1993) (2017-12-12)
Eva De Mol, Elzbieta Szulc, Claudio Di Sanza, Paula Martínez-Cristóbal, Carlos W Bertoncini, R Bryn Fenwick, Marta Frigolé-Vivas, Marianela Masín, Irene Hunter, Víctor Buzón, Isabelle Brun-Heath, Jesús García, Gianni De Fabritiis, Eva Estébanez-Perpiñá, Iain J McEwan, Ángel R Nebreda, Xavier Salvatella
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.

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