Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4
Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate that Smad4, together with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and ligand-binding domains, which may result in the modulation of 5α...
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| Veröffentlicht in: | The Journal of biological chemistry 2002-11, Vol.277 (46), p.43749-43756 |
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| container_title | The Journal of biological chemistry |
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| creator | Kang, Hong-Yo Huang, Ko-En Chang, Shiuh Young Ma, Wen-Lung Lin, Wen-Jye Chang, Chawnshang |
| description | Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate
that Smad4, together with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and ligand-binding domains,
which may result in the modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, in the prostate PC3
and LNCaP cells, addition of Smad3 can enhance AR transactivation, and co-transfection of Smad3 and Smad4 can then repress
AR transactivation in various androgen response element-promoter reporter assays as well as Northern blot and reverse transcription-PCR
quantitation assays with prostate-specific antigen mRNA expression. In contrast, in the SW480·C7 cells, lacking endogenous
functional Smad4, the influence of Smad3 on AR transactivation is dependent on the various androgen response element-promoters.
The influence of Smad3/Smad4 on the AR transactivation may involve the acetylation since the treatment of trichostatin A or
sodium butyrate can reverse Smad3/Smad4-repressed AR transactivation and Smad3/Smad4 complex can also decrease the acetylation
level of AR. Together, these results suggest that the interactions between AR, Smad3, and Smad4 may result in the differential
regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression. |
| doi_str_mv | 10.1074/jbc.M205603200 |
| format | Article |
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that Smad4, together with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and ligand-binding domains,
which may result in the modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, in the prostate PC3
and LNCaP cells, addition of Smad3 can enhance AR transactivation, and co-transfection of Smad3 and Smad4 can then repress
AR transactivation in various androgen response element-promoter reporter assays as well as Northern blot and reverse transcription-PCR
quantitation assays with prostate-specific antigen mRNA expression. In contrast, in the SW480·C7 cells, lacking endogenous
functional Smad4, the influence of Smad3 on AR transactivation is dependent on the various androgen response element-promoters.
The influence of Smad3/Smad4 on the AR transactivation may involve the acetylation since the treatment of trichostatin A or
sodium butyrate can reverse Smad3/Smad4-repressed AR transactivation and Smad3/Smad4 complex can also decrease the acetylation
level of AR. Together, these results suggest that the interactions between AR, Smad3, and Smad4 may result in the differential
regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M205603200</identifier><identifier>PMID: 12226080</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Blotting, Northern ; Blotting, Western ; Chloramphenicol O-Acetyltransferase - metabolism ; Dihydrotestosterone - metabolism ; DNA Primers - metabolism ; DNA-Binding Proteins - metabolism ; Genes, Tumor Suppressor ; Glutathione Transferase - metabolism ; Humans ; Ligands ; Male ; Models, Biological ; Precipitin Tests ; Prostatic Neoplasms - metabolism ; Protein Binding ; Receptors, Androgen - metabolism ; Recombinant Fusion Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Smad3 Protein ; Smad4 Protein ; Trans-Activators - metabolism ; Transcriptional Activation ; Transfection ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 2002-11, Vol.277 (46), p.43749-43756</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-b3a9124ee4da5cae0fad07d9468385c726fe5c4dd3b3e842219da22c7d031dd23</citedby><cites>FETCH-LOGICAL-c457t-b3a9124ee4da5cae0fad07d9468385c726fe5c4dd3b3e842219da22c7d031dd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12226080$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Hong-Yo</creatorcontrib><creatorcontrib>Huang, Ko-En</creatorcontrib><creatorcontrib>Chang, Shiuh Young</creatorcontrib><creatorcontrib>Ma, Wen-Lung</creatorcontrib><creatorcontrib>Lin, Wen-Jye</creatorcontrib><creatorcontrib>Chang, Chawnshang</creatorcontrib><title>Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate
that Smad4, together with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and ligand-binding domains,
which may result in the modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, in the prostate PC3
and LNCaP cells, addition of Smad3 can enhance AR transactivation, and co-transfection of Smad3 and Smad4 can then repress
AR transactivation in various androgen response element-promoter reporter assays as well as Northern blot and reverse transcription-PCR
quantitation assays with prostate-specific antigen mRNA expression. In contrast, in the SW480·C7 cells, lacking endogenous
functional Smad4, the influence of Smad3 on AR transactivation is dependent on the various androgen response element-promoters.
The influence of Smad3/Smad4 on the AR transactivation may involve the acetylation since the treatment of trichostatin A or
sodium butyrate can reverse Smad3/Smad4-repressed AR transactivation and Smad3/Smad4 complex can also decrease the acetylation
level of AR. Together, these results suggest that the interactions between AR, Smad3, and Smad4 may result in the differential
regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression.</description><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Chloramphenicol O-Acetyltransferase - metabolism</subject><subject>Dihydrotestosterone - metabolism</subject><subject>DNA Primers - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Genes, Tumor Suppressor</subject><subject>Glutathione Transferase - metabolism</subject><subject>Humans</subject><subject>Ligands</subject><subject>Male</subject><subject>Models, Biological</subject><subject>Precipitin Tests</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Protein Binding</subject><subject>Receptors, Androgen - metabolism</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Smad3 Protein</subject><subject>Smad4 Protein</subject><subject>Trans-Activators - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1P3DAQxS1EBQvlyhHlgLhlO_6KkyMCSiuBKhWQuFmOPWGNkjjYSSv--xrtShw7c5iR5jfv8B4hpxTWFJT49tra9T0DWQFnAHtkRaHmJZf0eZ-sABgtGybrQ3KU0ivkEg09IIeUMVZBDSvir33XYcRx9qYv7oNbejP7MBahKy5HF8MLjsVvtDjNIZYDOm9mdMVjNGMydvZ_tnT7XjwMxvHCjPm4DCEWD8s0RUzpY80n8ZV86Uyf8GQ3j8nT95vHqx_l3a_bn1eXd6UVUs1ly01DmUAUzkhrEDrjQLlGVDWvpVWs6lBa4RxvOdaCMdo4w5hVDjh1jvFjcrHVnWJ4WzDNevDJYt-bEcOSdFZQde7_grSWICSlGVxvQRtDShE7PUU_mPiuKeiPFHROQX-mkB_OdspLmy37xHe2Z-B8C2z8y-avj6hbH-wGB82U0qLSgivR8H_IN4_R</recordid><startdate>20021115</startdate><enddate>20021115</enddate><creator>Kang, Hong-Yo</creator><creator>Huang, Ko-En</creator><creator>Chang, Shiuh Young</creator><creator>Ma, Wen-Lung</creator><creator>Lin, Wen-Jye</creator><creator>Chang, Chawnshang</creator><general>American Society for Biochemistry and Molecular Biology</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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20021115</creationdate><title>Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4</title><author>Kang, Hong-Yo ; Huang, Ko-En ; Chang, Shiuh Young ; Ma, Wen-Lung ; Lin, Wen-Jye ; Chang, Chawnshang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-b3a9124ee4da5cae0fad07d9468385c726fe5c4dd3b3e842219da22c7d031dd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Chloramphenicol O-Acetyltransferase - metabolism</topic><topic>Dihydrotestosterone - metabolism</topic><topic>DNA Primers - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Genes, Tumor Suppressor</topic><topic>Glutathione Transferase - metabolism</topic><topic>Humans</topic><topic>Ligands</topic><topic>Male</topic><topic>Models, Biological</topic><topic>Precipitin Tests</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Protein Binding</topic><topic>Receptors, Androgen - metabolism</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Smad3 Protein</topic><topic>Smad4 Protein</topic><topic>Trans-Activators - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Hong-Yo</creatorcontrib><creatorcontrib>Huang, Ko-En</creatorcontrib><creatorcontrib>Chang, Shiuh Young</creatorcontrib><creatorcontrib>Ma, Wen-Lung</creatorcontrib><creatorcontrib>Lin, Wen-Jye</creatorcontrib><creatorcontrib>Chang, Chawnshang</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Hong-Yo</au><au>Huang, Ko-En</au><au>Chang, Shiuh Young</au><au>Ma, Wen-Lung</au><au>Lin, Wen-Jye</au><au>Chang, Chawnshang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-11-15</date><risdate>2002</risdate><volume>277</volume><issue>46</issue><spage>43749</spage><epage>43756</epage><pages>43749-43756</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate
that Smad4, together with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and ligand-binding domains,
which may result in the modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, in the prostate PC3
and LNCaP cells, addition of Smad3 can enhance AR transactivation, and co-transfection of Smad3 and Smad4 can then repress
AR transactivation in various androgen response element-promoter reporter assays as well as Northern blot and reverse transcription-PCR
quantitation assays with prostate-specific antigen mRNA expression. In contrast, in the SW480·C7 cells, lacking endogenous
functional Smad4, the influence of Smad3 on AR transactivation is dependent on the various androgen response element-promoters.
The influence of Smad3/Smad4 on the AR transactivation may involve the acetylation since the treatment of trichostatin A or
sodium butyrate can reverse Smad3/Smad4-repressed AR transactivation and Smad3/Smad4 complex can also decrease the acetylation
level of AR. Together, these results suggest that the interactions between AR, Smad3, and Smad4 may result in the differential
regulation of the AR transactivation, which further strengthens their roles in the prostate cancer progression.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>12226080</pmid><doi>10.1074/jbc.M205603200</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Blotting, Northern Blotting, Western Chloramphenicol O-Acetyltransferase - metabolism Dihydrotestosterone - metabolism DNA Primers - metabolism DNA-Binding Proteins - metabolism Genes, Tumor Suppressor Glutathione Transferase - metabolism Humans Ligands Male Models, Biological Precipitin Tests Prostatic Neoplasms - metabolism Protein Binding Receptors, Androgen - metabolism Recombinant Fusion Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Smad3 Protein Smad4 Protein Trans-Activators - metabolism Transcriptional Activation Transfection Tumor Cells, Cultured |
| title | Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4 |
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