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Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators.
- Source :
-
Structure (London, England : 1993) [Structure] 2018 Jan 02; Vol. 26 (1), pp. 145-152.e3. Date of Electronic Publication: 2017 Dec 07. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Motifs
Binding Sites
Cloning, Molecular
Crystallography, X-Ray
DNA genetics
DNA metabolism
Escherichia coli genetics
Escherichia coli metabolism
Gene Expression
Genetic Vectors chemistry
Genetic Vectors metabolism
HEK293 Cells
Humans
Intrinsically Disordered Proteins genetics
Intrinsically Disordered Proteins metabolism
Male
Models, Molecular
Prostatic Neoplasms, Castration-Resistant genetics
Prostatic Neoplasms, Castration-Resistant metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Receptors, Androgen genetics
Receptors, Androgen metabolism
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Transcription Factors, TFII genetics
Transcription Factors, TFII metabolism
Transcriptional Activation
DNA chemistry
Intrinsically Disordered Proteins chemistry
Receptors, Androgen chemistry
Transcription Factors, TFII chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-4186
- Volume :
- 26
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 29225078
- Full Text :
- https://doi.org/10.1016/j.str.2017.11.007