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Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP

The androgen receptor (AR) has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a tran...

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Autores principales: Elvenes, Julianne, Thomassen, Ernst Ivan Simon, Johnsen, Sylvia Sagen, Kaino, Katrine, Sjøttem, Eva, Johansen, Terje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174178/
https://www.ncbi.nlm.nih.gov/pubmed/21935435
http://dx.doi.org/10.1371/journal.pone.0024659
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author Elvenes, Julianne
Thomassen, Ernst Ivan Simon
Johnsen, Sylvia Sagen
Kaino, Katrine
Sjøttem, Eva
Johansen, Terje
author_facet Elvenes, Julianne
Thomassen, Ernst Ivan Simon
Johnsen, Sylvia Sagen
Kaino, Katrine
Sjøttem, Eva
Johansen, Terje
author_sort Elvenes, Julianne
collection PubMed
description The androgen receptor (AR) has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a transcriptional regulator that previously has been shown to enhance the activity of Pax6. In this study we have identified SPBP to act as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. Enhanced expression of Pax6 reduced the amount of SPBP associated with the probasin promoter when assayed by ChIP in HeLa cells. We mapped the interaction between both AR and SPBP, and AR and Pax6 to the DNA-binding domains of the involved proteins. Further binding studies revealed that Pax6 and SPBP compete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to molecular targeted drugs for treatment of prostate cancer.
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spelling pubmed-31741782011-09-20 Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP Elvenes, Julianne Thomassen, Ernst Ivan Simon Johnsen, Sylvia Sagen Kaino, Katrine Sjøttem, Eva Johansen, Terje PLoS One Research Article The androgen receptor (AR) has a central role in development and maintenance of the male reproductive system and in the etiology of prostate cancer. The transcription factor Pax6 has recently been reported to act as a repressor of AR and to be hypermethylated in prostate cancer cells. SPBP is a transcriptional regulator that previously has been shown to enhance the activity of Pax6. In this study we have identified SPBP to act as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. Enhanced expression of Pax6 reduced the amount of SPBP associated with the probasin promoter when assayed by ChIP in HeLa cells. We mapped the interaction between both AR and SPBP, and AR and Pax6 to the DNA-binding domains of the involved proteins. Further binding studies revealed that Pax6 and SPBP compete for binding to AR. These results suggest that Pax6 represses AR activity by displacing and/or inhibiting recruitment of coactivators to AR target promoters. Understanding the mechanism for inhibition of AR coactivators can give rise to molecular targeted drugs for treatment of prostate cancer. Public Library of Science 2011-09-15 /pmc/articles/PMC3174178/ /pubmed/21935435 http://dx.doi.org/10.1371/journal.pone.0024659 Text en Elvenes et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Elvenes, Julianne
Thomassen, Ernst Ivan Simon
Johnsen, Sylvia Sagen
Kaino, Katrine
Sjøttem, Eva
Johansen, Terje
Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title_full Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title_fullStr Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title_full_unstemmed Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title_short Pax6 Represses Androgen Receptor-Mediated Transactivation by Inhibiting Recruitment of the Coactivator SPBP
title_sort pax6 represses androgen receptor-mediated transactivation by inhibiting recruitment of the coactivator spbp
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174178/
https://www.ncbi.nlm.nih.gov/pubmed/21935435
http://dx.doi.org/10.1371/journal.pone.0024659
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