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Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D
The androgen receptor (AR) is a transcription factor that is pivotal for the development of prostate cancer. Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD...
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| Published in: | Biochemical and biophysical research communications 2007-08, Vol.359 (3), p.742-746 |
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| container_end_page | 746 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Shin, Sook Janknecht, Ralf |
| description | The androgen receptor (AR) is a transcription factor that is pivotal for the development of prostate cancer. Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD2A and JMJD2D. On the other hand, JMJD2A utilizes its catalytic domain or C-terminus to bind to AR, and JMJD2D does so via its C-terminus. Further, overexpression of JMJD2A or D stimulates AR function and this is dependent on JMJD2 catalytic activity. Conversely, downregulation of JMJD2A, which is often overexpressed in prostate tumors, reduces basal transcription of the AR target gene, prostate-specific antigen, in LNCaP prostate cancer cells. Altogether, our data have identified a novel class of AR coactivators, whose (over)expression in prostate tumors could contribute to the constitutive activation of AR and thus to androgen-depletion independency of advanced prostate cancer cells. |
| doi_str_mv | 10.1016/j.bbrc.2007.05.179 |
| format | article |
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Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD2A and JMJD2D. On the other hand, JMJD2A utilizes its catalytic domain or C-terminus to bind to AR, and JMJD2D does so via its C-terminus. Further, overexpression of JMJD2A or D stimulates AR function and this is dependent on JMJD2 catalytic activity. Conversely, downregulation of JMJD2A, which is often overexpressed in prostate tumors, reduces basal transcription of the AR target gene, prostate-specific antigen, in LNCaP prostate cancer cells. Altogether, our data have identified a novel class of AR coactivators, whose (over)expression in prostate tumors could contribute to the constitutive activation of AR and thus to androgen-depletion independency of advanced prostate cancer cells.</description><subject>Androgen receptor</subject><subject>Cell Line</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Histone demethylation</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>JmjC domain</subject><subject>JMJD2</subject><subject>JMJD2A</subject><subject>JMJD2D</subject><subject>Jumonji Domain-Containing Histone Demethylases</subject><subject>Oxidoreductases - metabolism</subject><subject>Oxidoreductases, N-Demethylating - genetics</subject><subject>Oxidoreductases, N-Demethylating - metabolism</subject><subject>Prostate cancer</subject><subject>Prostate-specific antigen</subject><subject>Protein Binding</subject><subject>Receptors, Androgen - genetics</subject><subject>Receptors, Androgen - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic - genetics</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqFkL1OwzAURi0EglJ4AQaUiS3h2ontWmKpKD9FIBaQ2CzbuQFXbVzstFLfnlStxAbTvcP5znAIuaBQUKDielZYG13BAGQBvKBSHZABBQU5o1AdkgEAiJwp-nFCTlOaAVBaCXVMTqjknEvKBmQ6dp1fm86HNgtNZto6hk9ss4gOl12Imd1kXz51ocWsxgV2X5u5SZiyp5enCRtvB7t3ckaOGjNPeL6_Q_J-f_d2-5g_vz5Mb8fPuas47XIpsGlAIDhby9KWjRyVwqFoTFVL6xizqlJCWu4Yp6ZEaVTdwAiMqKiSCsohudp5lzF8rzB1euGTw_nctBhWSUsQVPGS_Qv2ukqORqIH2Q50MaQUsdHL6BcmbjQFvS2tZ3pbWm9La-C6L92PLvf2lV1g_TvZp-2Bmx2AfYy1x6iT89g6rH0ft9N18H_5fwAeQo3Y</recordid><startdate>20070803</startdate><enddate>20070803</enddate><creator>Shin, Sook</creator><creator>Janknecht, Ralf</creator><general>Elsevier Inc</general><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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20070803</creationdate><title>Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D</title><author>Shin, Sook ; Janknecht, Ralf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-76eff06e0cbd73b3f7836ce6fa4d7bc22b94967b5c251a3e7a9df080a64197903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Androgen receptor</topic><topic>Cell Line</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Histone demethylation</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>JmjC domain</topic><topic>JMJD2</topic><topic>JMJD2A</topic><topic>JMJD2D</topic><topic>Jumonji Domain-Containing Histone Demethylases</topic><topic>Oxidoreductases - metabolism</topic><topic>Oxidoreductases, N-Demethylating - genetics</topic><topic>Oxidoreductases, N-Demethylating - metabolism</topic><topic>Prostate cancer</topic><topic>Prostate-specific antigen</topic><topic>Protein Binding</topic><topic>Receptors, Androgen - genetics</topic><topic>Receptors, Androgen - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin, Sook</creatorcontrib><creatorcontrib>Janknecht, Ralf</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shin, Sook</au><au>Janknecht, Ralf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2007-08-03</date><risdate>2007</risdate><volume>359</volume><issue>3</issue><spage>742</spage><epage>746</epage><pages>742-746</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>The androgen receptor (AR) is a transcription factor that is pivotal for the development of prostate cancer. Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD2A and JMJD2D. On the other hand, JMJD2A utilizes its catalytic domain or C-terminus to bind to AR, and JMJD2D does so via its C-terminus. Further, overexpression of JMJD2A or D stimulates AR function and this is dependent on JMJD2 catalytic activity. Conversely, downregulation of JMJD2A, which is often overexpressed in prostate tumors, reduces basal transcription of the AR target gene, prostate-specific antigen, in LNCaP prostate cancer cells. Altogether, our data have identified a novel class of AR coactivators, whose (over)expression in prostate tumors could contribute to the constitutive activation of AR and thus to androgen-depletion independency of advanced prostate cancer cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17555712</pmid><doi>10.1016/j.bbrc.2007.05.179</doi><tpages>5</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2007-08, Vol.359 (3), p.742-746 |
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| language | eng |
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| source | Elsevier |
| subjects | Androgen receptor Cell Line DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Histone demethylation Histones - metabolism Humans JmjC domain JMJD2 JMJD2A JMJD2D Jumonji Domain-Containing Histone Demethylases Oxidoreductases - metabolism Oxidoreductases, N-Demethylating - genetics Oxidoreductases, N-Demethylating - metabolism Prostate cancer Prostate-specific antigen Protein Binding Receptors, Androgen - genetics Receptors, Androgen - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic - genetics |
| title | Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D |
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