Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechani...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2010-03, Vol.285 (13), p.10122-10129 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 10129 |
|---|---|
| container_issue | 13 |
| container_start_page | 10122 |
| container_title | The Journal of biological chemistry |
| container_volume | 285 |
| creator | Goh, Yun-Mi Cinghu, Senthilkumar Hong, Eileen Tan Hwee Lee, You-Soub Kim, Jang-Hyun Jang, Ju-Won Li, Ying-Hui Chi, Xin-Zi Lee, Kyeong-Sook Wee, Heejun Ito, Yoshiaki Oh, Byung-Chul Bae, Suk-Chul |
| description | RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers. |
| doi_str_mv | 10.1074/jbc.M109.071381 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2843174</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925819550633</els_id><sourcerecordid>733792359</sourcerecordid><originalsourceid>FETCH-LOGICAL-c532t-f47a5b7a7706d773ef31955645fa07a20b3f1da5e4f61485961237c013a1a0903</originalsourceid><addsrcrecordid>eNp1kU1rGzEQhkVpady0597avfW0zsxqtVpdCsX0i7ofJDHkJsZabaywXrmSHHB-fWQ2De2hQiCGeead0byMvUaYI8j67GZt5t8R1Bwk8hafsBlCy0su8OopmwFUWKpKtCfsRYw3kE-t8Dk7qQAhc2LG9EUwxTc3UrTFr42Pu40Ph4GSjcX56scVLygVl4fgoxttcW6j6_Y5RWNXLL2hwd3lKG1ybfDJurHI9xguDsnvBorbl-xZT0O0rx7eU7b69PFy8aVc_vz8dfFhWRrBq1T2tSSxliQlNJ2U3PYclRBNLXoCSRWseY8dCVv3DdatUA1WXBpATkiggJ-y95Pubr_e2s7YMQUa9C64LYWD9uT0v5nRbfS1v9VVW3OUdRZ49yAQ_O_8x6S3Lho7DDRav49aci5VxYXK5NlEmryWGGz_2AVBH13R2RV9dEVPruSKN38P98j_sSEDbyegJ6_pOrioVxc5ywFbbBrVZEJNhM1LvHU26GicHY3tXLAm6c67_7a_B4IKpT0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733792359</pqid></control><display><type>article</type><title>Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Goh, Yun-Mi ; Cinghu, Senthilkumar ; Hong, Eileen Tan Hwee ; Lee, You-Soub ; Kim, Jang-Hyun ; Jang, Ju-Won ; Li, Ying-Hui ; Chi, Xin-Zi ; Lee, Kyeong-Sook ; Wee, Heejun ; Ito, Yoshiaki ; Oh, Byung-Chul ; Bae, Suk-Chul</creator><creatorcontrib>Goh, Yun-Mi ; Cinghu, Senthilkumar ; Hong, Eileen Tan Hwee ; Lee, You-Soub ; Kim, Jang-Hyun ; Jang, Ju-Won ; Li, Ying-Hui ; Chi, Xin-Zi ; Lee, Kyeong-Sook ; Wee, Heejun ; Ito, Yoshiaki ; Oh, Byung-Chul ; Bae, Suk-Chul</creatorcontrib><description>RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M109.071381</identifier><identifier>PMID: 20100835</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Breast Neoplasms - metabolism ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Core Binding Factor Alpha 3 Subunit - metabolism ; Cytoplasm - metabolism ; Diseases/Cancer ; Diseases/Cancer/Carcinogenesis ; Diseases/Cancer/Oncogene ; Gene Expression Regulation, Neoplastic ; HeLa Cells ; Humans ; Molecular Bases of Disease ; Oncogene ; Phosphorylation ; Protein Transport ; Protein/Post-translational Modification ; Protein/Protein-Protein Interactions ; Protein/Translocation ; RNA, Small Interfering - metabolism ; src-Family Kinases - metabolism ; Stomach Neoplasms - metabolism ; Tumor/Suppressor ; Tyrosine - chemistry ; Tyrosine - genetics ; Tyrosine - metabolism</subject><ispartof>The Journal of biological chemistry, 2010-03, Vol.285 (13), p.10122-10129</ispartof><rights>2010 © 2010 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2010 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-f47a5b7a7706d773ef31955645fa07a20b3f1da5e4f61485961237c013a1a0903</citedby><cites>FETCH-LOGICAL-c532t-f47a5b7a7706d773ef31955645fa07a20b3f1da5e4f61485961237c013a1a0903</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/PMC2843174/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843174/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20100835$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goh, Yun-Mi</creatorcontrib><creatorcontrib>Cinghu, Senthilkumar</creatorcontrib><creatorcontrib>Hong, Eileen Tan Hwee</creatorcontrib><creatorcontrib>Lee, You-Soub</creatorcontrib><creatorcontrib>Kim, Jang-Hyun</creatorcontrib><creatorcontrib>Jang, Ju-Won</creatorcontrib><creatorcontrib>Li, Ying-Hui</creatorcontrib><creatorcontrib>Chi, Xin-Zi</creatorcontrib><creatorcontrib>Lee, Kyeong-Sook</creatorcontrib><creatorcontrib>Wee, Heejun</creatorcontrib><creatorcontrib>Ito, Yoshiaki</creatorcontrib><creatorcontrib>Oh, Byung-Chul</creatorcontrib><creatorcontrib>Bae, Suk-Chul</creatorcontrib><title>Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.</description><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Core Binding Factor Alpha 3 Subunit - metabolism</subject><subject>Cytoplasm - metabolism</subject><subject>Diseases/Cancer</subject><subject>Diseases/Cancer/Carcinogenesis</subject><subject>Diseases/Cancer/Oncogene</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Molecular Bases of Disease</subject><subject>Oncogene</subject><subject>Phosphorylation</subject><subject>Protein Transport</subject><subject>Protein/Post-translational Modification</subject><subject>Protein/Protein-Protein Interactions</subject><subject>Protein/Translocation</subject><subject>RNA, Small Interfering - metabolism</subject><subject>src-Family Kinases - metabolism</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Tumor/Suppressor</subject><subject>Tyrosine - chemistry</subject><subject>Tyrosine - genetics</subject><subject>Tyrosine - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1rGzEQhkVpady0597avfW0zsxqtVpdCsX0i7ofJDHkJsZabaywXrmSHHB-fWQ2De2hQiCGeead0byMvUaYI8j67GZt5t8R1Bwk8hafsBlCy0su8OopmwFUWKpKtCfsRYw3kE-t8Dk7qQAhc2LG9EUwxTc3UrTFr42Pu40Ph4GSjcX56scVLygVl4fgoxttcW6j6_Y5RWNXLL2hwd3lKG1ybfDJurHI9xguDsnvBorbl-xZT0O0rx7eU7b69PFy8aVc_vz8dfFhWRrBq1T2tSSxliQlNJ2U3PYclRBNLXoCSRWseY8dCVv3DdatUA1WXBpATkiggJ-y95Pubr_e2s7YMQUa9C64LYWD9uT0v5nRbfS1v9VVW3OUdRZ49yAQ_O_8x6S3Lho7DDRav49aci5VxYXK5NlEmryWGGz_2AVBH13R2RV9dEVPruSKN38P98j_sSEDbyegJ6_pOrioVxc5ywFbbBrVZEJNhM1LvHU26GicHY3tXLAm6c67_7a_B4IKpT0</recordid><startdate>20100326</startdate><enddate>20100326</enddate><creator>Goh, Yun-Mi</creator><creator>Cinghu, Senthilkumar</creator><creator>Hong, Eileen Tan Hwee</creator><creator>Lee, You-Soub</creator><creator>Kim, Jang-Hyun</creator><creator>Jang, Ju-Won</creator><creator>Li, Ying-Hui</creator><creator>Chi, Xin-Zi</creator><creator>Lee, Kyeong-Sook</creator><creator>Wee, Heejun</creator><creator>Ito, Yoshiaki</creator><creator>Oh, Byung-Chul</creator><creator>Bae, Suk-Chul</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20100326</creationdate><title>Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm</title><author>Goh, Yun-Mi ; Cinghu, Senthilkumar ; Hong, Eileen Tan Hwee ; Lee, You-Soub ; Kim, Jang-Hyun ; Jang, Ju-Won ; Li, Ying-Hui ; Chi, Xin-Zi ; Lee, Kyeong-Sook ; Wee, Heejun ; Ito, Yoshiaki ; Oh, Byung-Chul ; Bae, Suk-Chul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-f47a5b7a7706d773ef31955645fa07a20b3f1da5e4f61485961237c013a1a0903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Core Binding Factor Alpha 3 Subunit - metabolism</topic><topic>Cytoplasm - metabolism</topic><topic>Diseases/Cancer</topic><topic>Diseases/Cancer/Carcinogenesis</topic><topic>Diseases/Cancer/Oncogene</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Molecular Bases of Disease</topic><topic>Oncogene</topic><topic>Phosphorylation</topic><topic>Protein Transport</topic><topic>Protein/Post-translational Modification</topic><topic>Protein/Protein-Protein Interactions</topic><topic>Protein/Translocation</topic><topic>RNA, Small Interfering - metabolism</topic><topic>src-Family Kinases - metabolism</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Tumor/Suppressor</topic><topic>Tyrosine - chemistry</topic><topic>Tyrosine - genetics</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goh, Yun-Mi</creatorcontrib><creatorcontrib>Cinghu, Senthilkumar</creatorcontrib><creatorcontrib>Hong, Eileen Tan Hwee</creatorcontrib><creatorcontrib>Lee, You-Soub</creatorcontrib><creatorcontrib>Kim, Jang-Hyun</creatorcontrib><creatorcontrib>Jang, Ju-Won</creatorcontrib><creatorcontrib>Li, Ying-Hui</creatorcontrib><creatorcontrib>Chi, Xin-Zi</creatorcontrib><creatorcontrib>Lee, Kyeong-Sook</creatorcontrib><creatorcontrib>Wee, Heejun</creatorcontrib><creatorcontrib>Ito, Yoshiaki</creatorcontrib><creatorcontrib>Oh, Byung-Chul</creatorcontrib><creatorcontrib>Bae, Suk-Chul</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goh, Yun-Mi</au><au>Cinghu, Senthilkumar</au><au>Hong, Eileen Tan Hwee</au><au>Lee, You-Soub</au><au>Kim, Jang-Hyun</au><au>Jang, Ju-Won</au><au>Li, Ying-Hui</au><au>Chi, Xin-Zi</au><au>Lee, Kyeong-Sook</au><au>Wee, Heejun</au><au>Ito, Yoshiaki</au><au>Oh, Byung-Chul</au><au>Bae, Suk-Chul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2010-03-26</date><risdate>2010</risdate><volume>285</volume><issue>13</issue><spage>10122</spage><epage>10129</epage><pages>10122-10129</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20100835</pmid><doi>10.1074/jbc.M109.071381</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2010-03, Vol.285 (13), p.10122-10129 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2843174 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Breast Neoplasms - metabolism Cell Line, Tumor Cell Nucleus - metabolism Core Binding Factor Alpha 3 Subunit - metabolism Cytoplasm - metabolism Diseases/Cancer Diseases/Cancer/Carcinogenesis Diseases/Cancer/Oncogene Gene Expression Regulation, Neoplastic HeLa Cells Humans Molecular Bases of Disease Oncogene Phosphorylation Protein Transport Protein/Post-translational Modification Protein/Protein-Protein Interactions Protein/Translocation RNA, Small Interfering - metabolism src-Family Kinases - metabolism Stomach Neoplasms - metabolism Tumor/Suppressor Tyrosine - chemistry Tyrosine - genetics Tyrosine - metabolism |
| title | Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T19%3A02%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Src%20Kinase%20Phosphorylates%20RUNX3%20at%20Tyrosine%20Residues%20and%20Localizes%20the%20Protein%20in%20the%20Cytoplasm&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Goh,%20Yun-Mi&rft.date=2010-03-26&rft.volume=285&rft.issue=13&rft.spage=10122&rft.epage=10129&rft.pages=10122-10129&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M109.071381&rft_dat=%3Cproquest_pubme%3E733792359%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733792359&rft_id=info:pmid/20100835&rft_els_id=S0021925819550633&rfr_iscdi=true |