Regulation of the androgen receptor by SET9-mediated methylation
The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that re...
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| Veröffentlicht in: | Nucleic acids research 2011-03, Vol.39 (4), p.1266-1279 |
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| creator | Gaughan, Luke Stockley, Jacqueline Wang, Nan McCracken, Stuart R.C Treumann, Achim Armstrong, Kelly Shaheen, Fadhel Watt, Kate McEwan, Iain J Wang, Chenguang Pestell, Richard G Robson, Craig N |
| description | The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment. |
| doi_str_mv | 10.1093/nar/gkq861 |
| format | Article |
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Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment.</description><identifier>ISSN: 0305-1048</identifier><identifier>ISSN: 1362-4962</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkq861</identifier><identifier>PMID: 20959290</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Active Transport, Cell Nucleus ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Cell Proliferation ; Gene Regulation, Chromatin and Epigenetics ; Histone-Lysine N-Methyltransferase - metabolism ; Histones - metabolism ; Humans ; Lysine - metabolism ; Male ; Methylation ; Prostate-Specific Antigen - genetics ; Prostatic Neoplasms - enzymology ; Receptors, Androgen - chemistry ; Receptors, Androgen - metabolism ; Transcriptional Activation</subject><ispartof>Nucleic acids research, 2011-03, Vol.39 (4), p.1266-1279</ispartof><rights>The Author(s) 2010. Published by Oxford University Press. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-cd7cd81628578016c6196e6d03120f5cc4de53a681522eff491edfe84af047da3</citedby><cites>FETCH-LOGICAL-c499t-cd7cd81628578016c6196e6d03120f5cc4de53a681522eff491edfe84af047da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045589/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045589/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20959290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaughan, Luke</creatorcontrib><creatorcontrib>Stockley, Jacqueline</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>McCracken, Stuart R.C</creatorcontrib><creatorcontrib>Treumann, Achim</creatorcontrib><creatorcontrib>Armstrong, Kelly</creatorcontrib><creatorcontrib>Shaheen, Fadhel</creatorcontrib><creatorcontrib>Watt, Kate</creatorcontrib><creatorcontrib>McEwan, Iain J</creatorcontrib><creatorcontrib>Wang, Chenguang</creatorcontrib><creatorcontrib>Pestell, Richard G</creatorcontrib><creatorcontrib>Robson, Craig N</creatorcontrib><title>Regulation of the androgen receptor by SET9-mediated methylation</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment.</description><subject>Active Transport, Cell Nucleus</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation</subject><subject>Gene Regulation, Chromatin and Epigenetics</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Lysine - metabolism</subject><subject>Male</subject><subject>Methylation</subject><subject>Prostate-Specific Antigen - genetics</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Receptors, Androgen - chemistry</subject><subject>Receptors, Androgen - metabolism</subject><subject>Transcriptional Activation</subject><issn>0305-1048</issn><issn>1362-4962</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rFEEQhhtRzCZ68Qfo3ARhTFV_bfdFlJCoEBBMcm463dWzo7PTm-5ZYf-9EyYGPXmqQz318hYPY68Q3iNYcTr6ctr9vDMan7AVCs1baTV_ylYgQLUI0hyx41p_AKBEJZ-zIw5WWW5hxT5-p24_-KnPY5NTM22o8WMsuaOxKRRoN-XS3B6aq_Nr224p9n6i2Gxp2hyWqxfsWfJDpZcP84TdXJxfn31pL799_nr26bIN0tqpDXEdokHNjVobQB00Wk06gkAOSYUgIynhtUHFOaUkLVJMZKRPINfRixP2Ycnd7W_nHoHGqfjB7Uq_9eXgsu_dv5ux37gu_3ICpFLGzgFvHwJKvttTndy2r4GGwY-U99VZWKMGFPBf0szY_ITmM_luIUPJtRZKj30Q3L0bN7txi5sZfv33B4_oHxkz8GYBks_Od6Wv7uaK31dCKy0YJX4DAsiUwg</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Gaughan, Luke</creator><creator>Stockley, Jacqueline</creator><creator>Wang, Nan</creator><creator>McCracken, Stuart R.C</creator><creator>Treumann, Achim</creator><creator>Armstrong, Kelly</creator><creator>Shaheen, Fadhel</creator><creator>Watt, Kate</creator><creator>McEwan, Iain J</creator><creator>Wang, Chenguang</creator><creator>Pestell, Richard G</creator><creator>Robson, Craig N</creator><general>Oxford University Press</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20110301</creationdate><title>Regulation of the androgen receptor by SET9-mediated methylation</title><author>Gaughan, Luke ; Stockley, Jacqueline ; Wang, Nan ; McCracken, Stuart R.C ; Treumann, Achim ; Armstrong, Kelly ; Shaheen, Fadhel ; Watt, Kate ; McEwan, Iain J ; Wang, Chenguang ; Pestell, Richard G ; Robson, Craig N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-cd7cd81628578016c6196e6d03120f5cc4de53a681522eff491edfe84af047da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation</topic><topic>Gene Regulation, Chromatin and Epigenetics</topic><topic>Histone-Lysine N-Methyltransferase - metabolism</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Lysine - metabolism</topic><topic>Male</topic><topic>Methylation</topic><topic>Prostate-Specific Antigen - genetics</topic><topic>Prostatic Neoplasms - enzymology</topic><topic>Receptors, Androgen - chemistry</topic><topic>Receptors, Androgen - metabolism</topic><topic>Transcriptional Activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gaughan, Luke</creatorcontrib><creatorcontrib>Stockley, Jacqueline</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>McCracken, Stuart R.C</creatorcontrib><creatorcontrib>Treumann, Achim</creatorcontrib><creatorcontrib>Armstrong, Kelly</creatorcontrib><creatorcontrib>Shaheen, Fadhel</creatorcontrib><creatorcontrib>Watt, Kate</creatorcontrib><creatorcontrib>McEwan, Iain J</creatorcontrib><creatorcontrib>Wang, Chenguang</creatorcontrib><creatorcontrib>Pestell, Richard G</creatorcontrib><creatorcontrib>Robson, Craig N</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaughan, Luke</au><au>Stockley, Jacqueline</au><au>Wang, Nan</au><au>McCracken, Stuart R.C</au><au>Treumann, Achim</au><au>Armstrong, Kelly</au><au>Shaheen, Fadhel</au><au>Watt, Kate</au><au>McEwan, Iain J</au><au>Wang, Chenguang</au><au>Pestell, Richard G</au><au>Robson, Craig N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of the androgen receptor by SET9-mediated methylation</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>39</volume><issue>4</issue><spage>1266</spage><epage>1279</epage><pages>1266-1279</pages><issn>0305-1048</issn><issn>1362-4962</issn><eissn>1362-4962</eissn><abstract>The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. 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| subjects | Active Transport, Cell Nucleus Cell Line, Tumor Cell Nucleus - metabolism Cell Proliferation Gene Regulation, Chromatin and Epigenetics Histone-Lysine N-Methyltransferase - metabolism Histones - metabolism Humans Lysine - metabolism Male Methylation Prostate-Specific Antigen - genetics Prostatic Neoplasms - enzymology Receptors, Androgen - chemistry Receptors, Androgen - metabolism Transcriptional Activation |
| title | Regulation of the androgen receptor by SET9-mediated methylation |
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