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http://hdl.handle.net/2445/53357
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DC Field | Value | Language |
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dc.contributor.author | Jehle, Katja | - |
dc.contributor.author | Cato, Laura | - |
dc.contributor.author | Neeb, Antje | - |
dc.contributor.author | Muhle-Goll, Claudia | - |
dc.contributor.author | Jung, Nicole | - |
dc.contributor.author | Smith, Emmanuel W. | - |
dc.contributor.author | Buzón Redorta, Víctor | - |
dc.contributor.author | Carbó, Laia R. | - |
dc.contributor.author | Estébanez Perpiñá, Eva | - |
dc.contributor.author | Schmitz, Katja | - |
dc.contributor.author | Fruk, Ljiljana | - |
dc.contributor.author | Chen, Yu | - |
dc.contributor.author | Cox, Marc B. | - |
dc.contributor.author | Brase, Stefan | - |
dc.contributor.author | Brown, Myles | - |
dc.contributor.author | Cato, Andrew C. B. | - |
dc.date.accessioned | 2014-04-08T12:33:22Z | - |
dc.date.available | 2014-04-08T12:33:22Z | - |
dc.date.issued | 2014-02-12 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/53357 | - |
dc.description.abstract | The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR. | - |
dc.format.extent | 37 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Versió postprint del document publicat a: http://dx.doi.org/10.1074/jbc.M113.534859 | - |
dc.relation.ispartof | Journal of Biological Chemistry, 2014, vol. 289, num. 13, p. 8839-8851 | - |
dc.relation.uri | http://dx.doi.org/10.1074/jbc.M113.534859 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2014 | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Receptors nuclears (Bioquímica) | - |
dc.subject.classification | Càncer de pròstata | - |
dc.subject.other | Nuclear receptors (Biochemistry) | - |
dc.subject.other | Prostate cancer | - |
dc.title | Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 619959 | - |
dc.date.updated | 2014-04-08T12:33:24Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24523409 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
Files in This Item:
File | Description | Size | Format | |
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619959.pdf | 5.95 MB | Adobe PDF | View/Open |
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