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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3174178?pdf=render |
| _version_ | 1819274228705263616 |
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| author | Julianne Elvenes Ernst Ivan Simon Thomassen Sylvia Sagen Johnsen Katrine Kaino Eva Sjøttem Terje Johansen |
| author_facet | Julianne Elvenes Ernst Ivan Simon Thomassen Sylvia Sagen Johnsen Katrine Kaino Eva Sjøttem Terje Johansen |
| author_sort | Julianne Elvenes |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T23:05:06Z |
| format | Article |
| id | doaj.art-7cbd8816b9f6472c935735fd4376c449 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T23:05:06Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7cbd8816b9f6472c935735fd4376c4492022-12-21T17:26:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2465910.1371/journal.pone.0024659Pax6 represses androgen receptor-mediated transactivation by inhibiting recruitment of the coactivator SPBP.Julianne ElvenesErnst Ivan Simon ThomassenSylvia Sagen JohnsenKatrine KainoEva SjøttemTerje JohansenThe 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.http://europepmc.org/articles/PMC3174178?pdf=render |
| spellingShingle | Julianne Elvenes Ernst Ivan Simon Thomassen Sylvia Sagen Johnsen Katrine Kaino Eva Sjøttem Terje Johansen Pax6 represses androgen receptor-mediated transactivation by inhibiting recruitment of the coactivator SPBP. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3174178?pdf=render |
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