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.
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 version of the paper has not been formally peer reviewed.
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