Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway
IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The...
Gespeichert in:
| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2006-01, Vol.66 (2), p.921-928 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 928 |
|---|---|
| container_issue | 2 |
| container_start_page | 921 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 66 |
| creator | DESAI, Shyamal D HAAS, Arthur L WOOD, Laurence M TSAI, Yu-Chen PESTKA, Sidney RUBIN, Eric H SALEEM, Ahamed NUR-E-KAMAL, Alam LIU, Leroy F |
| description | IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation. |
| doi_str_mv | 10.1158/0008-5472.CAN-05-1123 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70679576</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70679576</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4353-ce1da5f43ccf39e24a32d6e0309c84c0b6303aceb4ac787e80b736d09b6994163</originalsourceid><addsrcrecordid>eNpFkMtKxTAQhoMoerw8gpKN7qqT5tYu5eANRBfqOqbplBPp5ZikXt7eFg-6Gn74_pnhI-SYwTljsrgAgCKTQufny8uHDGTGWM63yIJJXmRaCLlNFn_MHtmP8W2KkoHcJXtMiVxArhbk9arFD5uwpvi1DhijH3o6NPTu6YZJ6nuaxm4I1GHbxikmDA1OGP30aUXTCulY-ffRJ99f5OqJrsOQ0MahQ7q2afVpvw_JTmPbiEebeUBerq-el7fZ_ePN3fLyPnOCS545ZLWVjeDONbzEXFie1wqBQ-kK4aBSHLh1WAnrdKGxgEpzVUNZqbIUTPEDcva7d3rhfcSYTOfj_LbtcRij0aB0KfUMyl_QhSHGgI1ZB9_Z8G0YmFmtmbWZWZuZ1BqQZlY79U42B8aqw_q_tXE5AacbwEZn2ybY3vn4z2klgRUl_wFQ5oGX</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70679576</pqid></control><display><type>article</type><title>Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><creator>DESAI, Shyamal D ; HAAS, Arthur L ; WOOD, Laurence M ; TSAI, Yu-Chen ; PESTKA, Sidney ; RUBIN, Eric H ; SALEEM, Ahamed ; NUR-E-KAMAL, Alam ; LIU, Leroy F</creator><creatorcontrib>DESAI, Shyamal D ; HAAS, Arthur L ; WOOD, Laurence M ; TSAI, Yu-Chen ; PESTKA, Sidney ; RUBIN, Eric H ; SALEEM, Ahamed ; NUR-E-KAMAL, Alam ; LIU, Leroy F</creatorcontrib><description>IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-05-1123</identifier><identifier>PMID: 16424026</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Biological and medical sciences ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cell Transformation, Neoplastic ; Cytokines - biosynthesis ; Cytokines - physiology ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Humans ; Molecular and cellular biology ; Proteasome Endopeptidase Complex - metabolism ; Proteins - metabolism ; RNA, Small Interfering ; Tumor Cells, Cultured ; Ubiquitin - metabolism ; Ubiquitins - biosynthesis ; Ubiquitins - physiology ; Up-Regulation</subject><ispartof>Cancer research (Chicago, Ill.), 2006-01, Vol.66 (2), p.921-928</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4353-ce1da5f43ccf39e24a32d6e0309c84c0b6303aceb4ac787e80b736d09b6994163</citedby><cites>FETCH-LOGICAL-c4353-ce1da5f43ccf39e24a32d6e0309c84c0b6303aceb4ac787e80b736d09b6994163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17650189$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16424026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DESAI, Shyamal D</creatorcontrib><creatorcontrib>HAAS, Arthur L</creatorcontrib><creatorcontrib>WOOD, Laurence M</creatorcontrib><creatorcontrib>TSAI, Yu-Chen</creatorcontrib><creatorcontrib>PESTKA, Sidney</creatorcontrib><creatorcontrib>RUBIN, Eric H</creatorcontrib><creatorcontrib>SALEEM, Ahamed</creatorcontrib><creatorcontrib>NUR-E-KAMAL, Alam</creatorcontrib><creatorcontrib>LIU, Leroy F</creatorcontrib><title>Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation.</description><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - physiology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Molecular and cellular biology</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteins - metabolism</subject><subject>RNA, Small Interfering</subject><subject>Tumor Cells, Cultured</subject><subject>Ubiquitin - metabolism</subject><subject>Ubiquitins - biosynthesis</subject><subject>Ubiquitins - physiology</subject><subject>Up-Regulation</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtKxTAQhoMoerw8gpKN7qqT5tYu5eANRBfqOqbplBPp5ZikXt7eFg-6Gn74_pnhI-SYwTljsrgAgCKTQufny8uHDGTGWM63yIJJXmRaCLlNFn_MHtmP8W2KkoHcJXtMiVxArhbk9arFD5uwpvi1DhijH3o6NPTu6YZJ6nuaxm4I1GHbxikmDA1OGP30aUXTCulY-ffRJ99f5OqJrsOQ0MahQ7q2afVpvw_JTmPbiEebeUBerq-el7fZ_ePN3fLyPnOCS545ZLWVjeDONbzEXFie1wqBQ-kK4aBSHLh1WAnrdKGxgEpzVUNZqbIUTPEDcva7d3rhfcSYTOfj_LbtcRij0aB0KfUMyl_QhSHGgI1ZB9_Z8G0YmFmtmbWZWZuZ1BqQZlY79U42B8aqw_q_tXE5AacbwEZn2ybY3vn4z2klgRUl_wFQ5oGX</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>DESAI, Shyamal D</creator><creator>HAAS, Arthur L</creator><creator>WOOD, Laurence M</creator><creator>TSAI, Yu-Chen</creator><creator>PESTKA, Sidney</creator><creator>RUBIN, Eric H</creator><creator>SALEEM, Ahamed</creator><creator>NUR-E-KAMAL, Alam</creator><creator>LIU, Leroy F</creator><general>American Association for Cancer Research</general><scope>IQODW</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></search><sort><creationdate>20060115</creationdate><title>Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway</title><author>DESAI, Shyamal D ; HAAS, Arthur L ; WOOD, Laurence M ; TSAI, Yu-Chen ; PESTKA, Sidney ; RUBIN, Eric H ; SALEEM, Ahamed ; NUR-E-KAMAL, Alam ; LIU, Leroy F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4353-ce1da5f43ccf39e24a32d6e0309c84c0b6303aceb4ac787e80b736d09b6994163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cell Transformation, Neoplastic</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - physiology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Molecular and cellular biology</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteins - metabolism</topic><topic>RNA, Small Interfering</topic><topic>Tumor Cells, Cultured</topic><topic>Ubiquitin - metabolism</topic><topic>Ubiquitins - biosynthesis</topic><topic>Ubiquitins - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DESAI, Shyamal D</creatorcontrib><creatorcontrib>HAAS, Arthur L</creatorcontrib><creatorcontrib>WOOD, Laurence M</creatorcontrib><creatorcontrib>TSAI, Yu-Chen</creatorcontrib><creatorcontrib>PESTKA, Sidney</creatorcontrib><creatorcontrib>RUBIN, Eric H</creatorcontrib><creatorcontrib>SALEEM, Ahamed</creatorcontrib><creatorcontrib>NUR-E-KAMAL, Alam</creatorcontrib><creatorcontrib>LIU, Leroy F</creatorcontrib><collection>Pascal-Francis</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><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DESAI, Shyamal D</au><au>HAAS, Arthur L</au><au>WOOD, Laurence M</au><au>TSAI, Yu-Chen</au><au>PESTKA, Sidney</au><au>RUBIN, Eric H</au><au>SALEEM, Ahamed</au><au>NUR-E-KAMAL, Alam</au><au>LIU, Leroy F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2006-01-15</date><risdate>2006</risdate><volume>66</volume><issue>2</issue><spage>921</spage><epage>928</epage><pages>921-928</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16424026</pmid><doi>10.1158/0008-5472.CAN-05-1123</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2006-01, Vol.66 (2), p.921-928 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70679576 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - pathology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic Cytokines - biosynthesis Cytokines - physiology Female Fundamental and applied biological sciences. Psychology Gene Expression Profiling Humans Molecular and cellular biology Proteasome Endopeptidase Complex - metabolism Proteins - metabolism RNA, Small Interfering Tumor Cells, Cultured Ubiquitin - metabolism Ubiquitins - biosynthesis Ubiquitins - physiology Up-Regulation |
| title | Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T17%3A56%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Elevated%20expression%20of%20ISG15%20in%20tumor%20cells%20interferes%20with%20the%20ubiquitin/26S%20proteasome%20pathway&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=DESAI,%20Shyamal%20D&rft.date=2006-01-15&rft.volume=66&rft.issue=2&rft.spage=921&rft.epage=928&rft.pages=921-928&rft.issn=0008-5472&rft.eissn=1538-7445&rft.coden=CNREA8&rft_id=info:doi/10.1158/0008-5472.CAN-05-1123&rft_dat=%3Cproquest_cross%3E70679576%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70679576&rft_id=info:pmid/16424026&rfr_iscdi=true |