Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis
SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by vira...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-10, Vol.104 (43), p.17028-17033 |
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| container_issue | 43 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Park, Junsoo Kim, Kwangsoo Lee, Eun-Ju Seo, Yun-Jee Lim, Si-Nae Park, Kyoungsook Rho, Seung Bae Lee, Seung-Hoon Lee, Je-Ho |
| description | SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently, SUMOylated IRF-1 displays enhanced resistance to degradation. SUMOylation of IRF-1 attenuates its transcription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response. |
| doi_str_mv | 10.1073/pnas.0609852104 |
| format | Article |
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This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently, SUMOylated IRF-1 displays enhanced resistance to degradation. SUMOylation of IRF-1 attenuates its transcription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0609852104</identifier><identifier>PMID: 17942705</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Antibodies ; Apoptosis ; Biological Sciences ; Cell Line, Tumor ; Cell lines ; Cells ; Gene expression ; HEK293 cells ; HeLa cells ; Humans ; Interferon ; Interferon Regulatory Factor-1 - metabolism ; Mutation ; Neoplasms - metabolism ; Neoplasms - pathology ; Plasmids ; Protein Processing, Post-Translational ; Protein stability ; Proteins ; Small Ubiquitin-Related Modifier Proteins - metabolism ; Thermodynamics ; Transcription, Genetic ; Tumor cell line ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-10, Vol.104 (43), p.17028-17033</ispartof><rights>Copyright 2007 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 23, 2007</rights><rights>2007 by The National Academy of Sciences of the USA 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4694-b37f7e3e3032145fc427fb436ff0c82cf6f6d9d10c2efc99452c1a212d4b31bb3</citedby><cites>FETCH-LOGICAL-c4694-b37f7e3e3032145fc427fb436ff0c82cf6f6d9d10c2efc99452c1a212d4b31bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/43.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25450176$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25450176$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17942705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Junsoo</creatorcontrib><creatorcontrib>Kim, Kwangsoo</creatorcontrib><creatorcontrib>Lee, Eun-Ju</creatorcontrib><creatorcontrib>Seo, Yun-Jee</creatorcontrib><creatorcontrib>Lim, Si-Nae</creatorcontrib><creatorcontrib>Park, Kyoungsook</creatorcontrib><creatorcontrib>Rho, Seung Bae</creatorcontrib><creatorcontrib>Lee, Seung-Hoon</creatorcontrib><creatorcontrib>Lee, Je-Ho</creatorcontrib><title>Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently, SUMOylated IRF-1 displays enhanced resistance to degradation. SUMOylation of IRF-1 attenuates its transcription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biological Sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Gene expression</subject><subject>HEK293 cells</subject><subject>HeLa cells</subject><subject>Humans</subject><subject>Interferon</subject><subject>Interferon Regulatory Factor-1 - metabolism</subject><subject>Mutation</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Plasmids</subject><subject>Protein Processing, Post-Translational</subject><subject>Protein stability</subject><subject>Proteins</subject><subject>Small Ubiquitin-Related Modifier Proteins - metabolism</subject><subject>Thermodynamics</subject><subject>Transcription, Genetic</subject><subject>Tumor cell line</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1v1DAQxS0EokvhzAmIOCBxSDv-iGNfkKqqhUpFldruhYvlOHabVTYOttPS_x5vs-oCF04je37zNE9vEHqL4QBDTQ_HQccD4CBFRTCwZ2iBQeKSMwnP0QKA1KVghO2hVzGuAEBWAl6iPVxLRmqoFujHSW_vdLJtkavtC--Kq-X3i4f-8e_s8rTERTcUaVr7UBjb9zE_kw3OBhuL-y7dzlC5tm33OKNHPyYfu_gavXC6j_bNtu6j5enJ9fG38vzi69nx0XlpGJesbGjtakstBUowq5zJm7mGUe4cGEGM4463ssVgiHVGSlYRgzXBpGUNxU1D99GXWXecmryFsUMKuldj6NY6PCivO_V3Z-hu1Y2_UwQYMEKywKetQPA_JxuTWndx41UP1k9RYSkEhxpn8OM_4MpPYcjmshZmhAvCMnQ4Qyb4GIN1T5tgUJvQ1CY0tQstT7z_08CO36aUgc9bYDO5k2OK0UwBEcpNfZ_sr5TZ4j9sRt7NyComH54YUrEKcM1z_8Pcd9orfRO6qJZX2SAFECSfEKa_Acz2vaw</recordid><startdate>20071023</startdate><enddate>20071023</enddate><creator>Park, Junsoo</creator><creator>Kim, Kwangsoo</creator><creator>Lee, Eun-Ju</creator><creator>Seo, Yun-Jee</creator><creator>Lim, Si-Nae</creator><creator>Park, Kyoungsook</creator><creator>Rho, Seung Bae</creator><creator>Lee, Seung-Hoon</creator><creator>Lee, Je-Ho</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</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>5PM</scope></search><sort><creationdate>20071023</creationdate><title>Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis</title><author>Park, Junsoo ; Kim, Kwangsoo ; Lee, Eun-Ju ; Seo, Yun-Jee ; Lim, Si-Nae ; Park, Kyoungsook ; Rho, Seung Bae ; Lee, Seung-Hoon ; Lee, Je-Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4694-b37f7e3e3032145fc427fb436ff0c82cf6f6d9d10c2efc99452c1a212d4b31bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biological Sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cells</topic><topic>Gene expression</topic><topic>HEK293 cells</topic><topic>HeLa cells</topic><topic>Humans</topic><topic>Interferon</topic><topic>Interferon Regulatory Factor-1 - metabolism</topic><topic>Mutation</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Plasmids</topic><topic>Protein Processing, Post-Translational</topic><topic>Protein stability</topic><topic>Proteins</topic><topic>Small Ubiquitin-Related Modifier Proteins - metabolism</topic><topic>Thermodynamics</topic><topic>Transcription, Genetic</topic><topic>Tumor cell line</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Junsoo</creatorcontrib><creatorcontrib>Kim, Kwangsoo</creatorcontrib><creatorcontrib>Lee, Eun-Ju</creatorcontrib><creatorcontrib>Seo, Yun-Jee</creatorcontrib><creatorcontrib>Lim, Si-Nae</creatorcontrib><creatorcontrib>Park, Kyoungsook</creatorcontrib><creatorcontrib>Rho, Seung Bae</creatorcontrib><creatorcontrib>Lee, Seung-Hoon</creatorcontrib><creatorcontrib>Lee, Je-Ho</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors 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>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Junsoo</au><au>Kim, Kwangsoo</au><au>Lee, Eun-Ju</au><au>Seo, Yun-Jee</au><au>Lim, Si-Nae</au><au>Park, Kyoungsook</au><au>Rho, Seung Bae</au><au>Lee, Seung-Hoon</au><au>Lee, Je-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2007-10-23</date><risdate>2007</risdate><volume>104</volume><issue>43</issue><spage>17028</spage><epage>17033</epage><pages>17028-17033</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently, SUMOylated IRF-1 displays enhanced resistance to degradation. SUMOylation of IRF-1 attenuates its transcription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17942705</pmid><doi>10.1073/pnas.0609852104</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Apoptosis Biological Sciences Cell Line, Tumor Cell lines Cells Gene expression HEK293 cells HeLa cells Humans Interferon Interferon Regulatory Factor-1 - metabolism Mutation Neoplasms - metabolism Neoplasms - pathology Plasmids Protein Processing, Post-Translational Protein stability Proteins Small Ubiquitin-Related Modifier Proteins - metabolism Thermodynamics Transcription, Genetic Tumor cell line Tumors |
| title | Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis |
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