Androgen receptor function is modulated by the tissue‐specific AR45 variant
A naturally occurring variant of the human androgen receptor (AR) named AR45 has been identified. It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA‐binding domain, hinge region and ligand‐binding domain, preceded by a novel seven amino‐acid long N‐terminal ext...
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Veröffentlicht in: | The FEBS journal 2005-01, Vol.272 (1), p.74-84 |
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description | A naturally occurring variant of the human androgen receptor (AR) named AR45 has been identified. It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA‐binding domain, hinge region and ligand‐binding domain, preceded by a novel seven amino‐acid long N‐terminal extension. A survey of human tissues revealed that AR45 was expressed mainly in heart and skeletal muscle. In cotransfection experiments, AR45 inhibited AR function, an effect necessitating intact DNA‐ and ligand‐binding properties. Overexpression of AR45 reduced the proliferation rate of the androgen‐dependent LNCaP cells, in line with the repressive effects of AR45 on AR growth‐promoting function. AR45 interacted with the AR N‐terminal domain in two‐hybrid assays, suggesting that AR inhibition was due to the formation of AR–AR45 heterodimers. Under conditions where the transcriptional coactivator TIF2 or the oncogene β‐catenin were overexpressed, AR45 stimulated androgen‐dependent promoters in presence of dihydrotestosterone. AR45 activity was triggered additionally by the adrenal androgen androstenedione in presence of exogenous TIF2. Altogether, the data suggest an important role of AR45 in modulating AR function and add a novel level of complexity to the mode of action of androgens. |
doi_str_mv | 10.1111/j.1432-1033.2004.04395.x |
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It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA‐binding domain, hinge region and ligand‐binding domain, preceded by a novel seven amino‐acid long N‐terminal extension. A survey of human tissues revealed that AR45 was expressed mainly in heart and skeletal muscle. In cotransfection experiments, AR45 inhibited AR function, an effect necessitating intact DNA‐ and ligand‐binding properties. Overexpression of AR45 reduced the proliferation rate of the androgen‐dependent LNCaP cells, in line with the repressive effects of AR45 on AR growth‐promoting function. AR45 interacted with the AR N‐terminal domain in two‐hybrid assays, suggesting that AR inhibition was due to the formation of AR–AR45 heterodimers. Under conditions where the transcriptional coactivator TIF2 or the oncogene β‐catenin were overexpressed, AR45 stimulated androgen‐dependent promoters in presence of dihydrotestosterone. AR45 activity was triggered additionally by the adrenal androgen androstenedione in presence of exogenous TIF2. 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It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA‐binding domain, hinge region and ligand‐binding domain, preceded by a novel seven amino‐acid long N‐terminal extension. A survey of human tissues revealed that AR45 was expressed mainly in heart and skeletal muscle. In cotransfection experiments, AR45 inhibited AR function, an effect necessitating intact DNA‐ and ligand‐binding properties. Overexpression of AR45 reduced the proliferation rate of the androgen‐dependent LNCaP cells, in line with the repressive effects of AR45 on AR growth‐promoting function. AR45 interacted with the AR N‐terminal domain in two‐hybrid assays, suggesting that AR inhibition was due to the formation of AR–AR45 heterodimers. Under conditions where the transcriptional coactivator TIF2 or the oncogene β‐catenin were overexpressed, AR45 stimulated androgen‐dependent promoters in presence of dihydrotestosterone. AR45 activity was triggered additionally by the adrenal androgen androstenedione in presence of exogenous TIF2. Altogether, the data suggest an important role of AR45 in modulating AR function and add a novel level of complexity to the mode of action of androgens.</description><subject>Amino Acid Sequence</subject><subject>androgen receptor</subject><subject>Base Sequence</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>cofactor</subject><subject>DNA Primers</subject><subject>heart</subject><subject>Humans</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Myocardium - metabolism</subject><subject>prostate</subject><subject>Receptors, Androgen - chemistry</subject><subject>Receptors, Androgen - metabolism</subject><subject>Receptors, Androgen - physiology</subject><subject>Transcription, Genetic</subject><issn>1742-464X</issn><issn>1742-4658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1q3DAQx0VJaL76CkX0kJsdfYxk-1LYLPmChECbQG9CtketFq-9kew0e-sj9Bn7JLGzSwM5ZS4zh9_8mfkRQjlL-Vgni5SDFAlnUqaCMUgZyEKlTx_IPs9AJKBVvvN_hh975CDGBWNSQVF8JHtcaQlSyn1yM2vr0P3ElgascNV3gbqhrXrftdRHuuzqobE91rRc0_4X0t7HOOC_P3_jCivvfEVn30DRRxu8bfsjsutsE_HTth-S-_Ozu_llcn17cTWfXScVgFLJ-IKoLStzp0GgkAXXZaVzZ0WJgHUtXYa8zmWmZJFxJ7BkonQ2U1xo6zTKQ3K8yV2F7mHA2JuljxU2jW2xG6LRmQTIeDaCX96Ai24I7XibEQw48ELoEco3UBW6GAM6swp-acPacGYm32ZhJt9m8m0m3-bFt3kaVz9v84dyifXr4lbwCHzdAL99g-t3B5vzs9Pv0yifAdH6juc</recordid><startdate>200501</startdate><enddate>200501</enddate><creator>Ahrens‐Fath, Isabelle</creator><creator>Politz, Oliver</creator><creator>Geserick, Christoph</creator><creator>Haendler, Bernard</creator><general>Blackwell Science Ltd</general><general>Blackwell Publishing Ltd</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200501</creationdate><title>Androgen receptor function is modulated by the tissue‐specific AR45 variant</title><author>Ahrens‐Fath, Isabelle ; Politz, Oliver ; Geserick, Christoph ; Haendler, Bernard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4455-1112da0b8f642e23916bc68fa2be4edd3f7e1d83753971f2eb02bfa75126af6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amino Acid Sequence</topic><topic>androgen receptor</topic><topic>Base Sequence</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>cofactor</topic><topic>DNA Primers</topic><topic>heart</topic><topic>Humans</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Myocardium - metabolism</topic><topic>prostate</topic><topic>Receptors, Androgen - chemistry</topic><topic>Receptors, Androgen - metabolism</topic><topic>Receptors, Androgen - physiology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahrens‐Fath, Isabelle</creatorcontrib><creatorcontrib>Politz, Oliver</creatorcontrib><creatorcontrib>Geserick, Christoph</creatorcontrib><creatorcontrib>Haendler, Bernard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The FEBS journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahrens‐Fath, Isabelle</au><au>Politz, Oliver</au><au>Geserick, Christoph</au><au>Haendler, Bernard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Androgen receptor function is modulated by the tissue‐specific AR45 variant</atitle><jtitle>The FEBS journal</jtitle><addtitle>FEBS J</addtitle><date>2005-01</date><risdate>2005</risdate><volume>272</volume><issue>1</issue><spage>74</spage><epage>84</epage><pages>74-84</pages><issn>1742-464X</issn><eissn>1742-4658</eissn><abstract>A naturally occurring variant of the human androgen receptor (AR) named AR45 has been identified. It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA‐binding domain, hinge region and ligand‐binding domain, preceded by a novel seven amino‐acid long N‐terminal extension. A survey of human tissues revealed that AR45 was expressed mainly in heart and skeletal muscle. In cotransfection experiments, AR45 inhibited AR function, an effect necessitating intact DNA‐ and ligand‐binding properties. Overexpression of AR45 reduced the proliferation rate of the androgen‐dependent LNCaP cells, in line with the repressive effects of AR45 on AR growth‐promoting function. AR45 interacted with the AR N‐terminal domain in two‐hybrid assays, suggesting that AR inhibition was due to the formation of AR–AR45 heterodimers. Under conditions where the transcriptional coactivator TIF2 or the oncogene β‐catenin were overexpressed, AR45 stimulated androgen‐dependent promoters in presence of dihydrotestosterone. AR45 activity was triggered additionally by the adrenal androgen androstenedione in presence of exogenous TIF2. Altogether, the data suggest an important role of AR45 in modulating AR function and add a novel level of complexity to the mode of action of androgens.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15634333</pmid><doi>10.1111/j.1432-1033.2004.04395.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence androgen receptor Base Sequence Cell Line Cell Proliferation cofactor DNA Primers heart Humans Male Molecular Sequence Data Myocardium - metabolism prostate Receptors, Androgen - chemistry Receptors, Androgen - metabolism Receptors, Androgen - physiology Transcription, Genetic |
title | Androgen receptor function is modulated by the tissue‐specific AR45 variant |
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