Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells
Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms α and/or β is associated with decreased nuclear and increased cytoplasmic topo IIα. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both iso...
Gespeichert in:
| Veröffentlicht in: | Experimental cell research 2007-02, Vol.313 (3), p.627-637 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 637 |
|---|---|
| container_issue | 3 |
| container_start_page | 627 |
| container_title | Experimental cell research |
| container_volume | 313 |
| creator | Mirski, Shelagh E.L. Sparks, Kathryn E. Friedrich, Beate Köhler, Matthias Mo, Yin-Yuan Beck, William T. Cole, Susan P.C. |
| description | Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms α and/or β is associated with decreased nuclear and increased cytoplasmic topo IIα. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both isoforms. In this study, we show that topo II α and β bind and are imported into the nucleus by importin α1, α3, and α5 in conjunction with importin β. Topo IIα also binds exportin/CRM1 in vitro. However, wild-type topo IIα has only been observed in the cytoplasm of cells that are entering plateau phase growth. This suggests that topo IIα may shuttle between the nucleus and the cytoplasm with the equilibrium towards the nucleus in proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1 inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo IIα with a mutant NLS, suggesting that its export is being inhibited. However, homokaryon shuttling experiments indicate that fluorescence-tagged wild-type topo II α and β proteins do not shuttle in proliferating Cos-1 or HeLa cells. We conclude that topo II α and β nuclear export is inhibited in proliferating cells so that these proteins do not shuttle. |
| doi_str_mv | 10.1016/j.yexcr.2006.11.004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68981971</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014482706004629</els_id><sourcerecordid>68981971</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-3cf384e4b0ea193b6e9d1bb9b3b6d947e510ce72900b1dd34efb43fc44ca8f153</originalsourceid><addsrcrecordid>eNp9UcuO1DAQtBCIHRa-AAn5xC3Z7sSTx4EDGgE70iIktJyt2O6wHiVxsJ1l5xv4Gn6Eb1oPGYkbp26pq6qruxh7jZAjYHV1yI_0oH1eAFQ5Yg4gnrANQgtZIYriKdsAoMhEU9QX7EUIBwBoGqyeswussSmgFBv269bNzgY3ku8C8f2eKzuZwO04Ox_txP_85mncOz8G3k2G08M6uNp9_YxcLZEbR4FPLvJwt8Q4EFcUfxJNPN4RnxY90LJS9TG6eejCyJPu7N1g-7Q1aX3nmoYhvGTP-m4I9OpcL9m3jx9ud9fZzZdP-937m0yX2zpmpe7LRpBQQB22paqoNahUq1JrWlHTFkFTXbQACo0pBfVKlL0WQndNj9vykr1ddZOHHwuFKEcbTg66idwSZNW0DbY1JmC5ArV3IXjq5ezt2PmjRJCnDORB_s1AnjKQiDJlkFhvzvKLGsn845yfngDvVgClI-8teRm0pUmTsZ50lMbZ_y54BORunUo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68981971</pqid></control><display><type>article</type><title>Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Mirski, Shelagh E.L. ; Sparks, Kathryn E. ; Friedrich, Beate ; Köhler, Matthias ; Mo, Yin-Yuan ; Beck, William T. ; Cole, Susan P.C.</creator><creatorcontrib>Mirski, Shelagh E.L. ; Sparks, Kathryn E. ; Friedrich, Beate ; Köhler, Matthias ; Mo, Yin-Yuan ; Beck, William T. ; Cole, Susan P.C.</creatorcontrib><description>Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms α and/or β is associated with decreased nuclear and increased cytoplasmic topo IIα. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both isoforms. In this study, we show that topo II α and β bind and are imported into the nucleus by importin α1, α3, and α5 in conjunction with importin β. Topo IIα also binds exportin/CRM1 in vitro. However, wild-type topo IIα has only been observed in the cytoplasm of cells that are entering plateau phase growth. This suggests that topo IIα may shuttle between the nucleus and the cytoplasm with the equilibrium towards the nucleus in proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1 inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo IIα with a mutant NLS, suggesting that its export is being inhibited. However, homokaryon shuttling experiments indicate that fluorescence-tagged wild-type topo II α and β proteins do not shuttle in proliferating Cos-1 or HeLa cells. We conclude that topo II α and β nuclear export is inhibited in proliferating cells so that these proteins do not shuttle.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2006.11.004</identifier><identifier>PMID: 17182034</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>alpha Karyopherins - metabolism ; Animals ; Cell Line ; Cell Nucleus - metabolism ; Cell Proliferation ; Chlorocebus aethiops ; COS Cells ; CRM1 ; Cytoplasm - metabolism ; DNA topoisomerase II ; DNA Topoisomerases, Type II - metabolism ; Exportin 1 Protein ; HeLa Cells ; Humans ; Importin α ; Karyopherins - metabolism ; Nuclear export ; Nuclear import ; Nuclear localization ; Nucleocytoplasmic shuttling ; Protein Isoforms ; Protein Transport ; Receptors, Cytoplasmic and Nuclear - metabolism ; Transfection</subject><ispartof>Experimental cell research, 2007-02, Vol.313 (3), p.627-637</ispartof><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-3cf384e4b0ea193b6e9d1bb9b3b6d947e510ce72900b1dd34efb43fc44ca8f153</citedby><cites>FETCH-LOGICAL-c357t-3cf384e4b0ea193b6e9d1bb9b3b6d947e510ce72900b1dd34efb43fc44ca8f153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014482706004629$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17182034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mirski, Shelagh E.L.</creatorcontrib><creatorcontrib>Sparks, Kathryn E.</creatorcontrib><creatorcontrib>Friedrich, Beate</creatorcontrib><creatorcontrib>Köhler, Matthias</creatorcontrib><creatorcontrib>Mo, Yin-Yuan</creatorcontrib><creatorcontrib>Beck, William T.</creatorcontrib><creatorcontrib>Cole, Susan P.C.</creatorcontrib><title>Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms α and/or β is associated with decreased nuclear and increased cytoplasmic topo IIα. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both isoforms. In this study, we show that topo II α and β bind and are imported into the nucleus by importin α1, α3, and α5 in conjunction with importin β. Topo IIα also binds exportin/CRM1 in vitro. However, wild-type topo IIα has only been observed in the cytoplasm of cells that are entering plateau phase growth. This suggests that topo IIα may shuttle between the nucleus and the cytoplasm with the equilibrium towards the nucleus in proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1 inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo IIα with a mutant NLS, suggesting that its export is being inhibited. However, homokaryon shuttling experiments indicate that fluorescence-tagged wild-type topo II α and β proteins do not shuttle in proliferating Cos-1 or HeLa cells. We conclude that topo II α and β nuclear export is inhibited in proliferating cells so that these proteins do not shuttle.</description><subject>alpha Karyopherins - metabolism</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>CRM1</subject><subject>Cytoplasm - metabolism</subject><subject>DNA topoisomerase II</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>Exportin 1 Protein</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Importin α</subject><subject>Karyopherins - metabolism</subject><subject>Nuclear export</subject><subject>Nuclear import</subject><subject>Nuclear localization</subject><subject>Nucleocytoplasmic shuttling</subject><subject>Protein Isoforms</subject><subject>Protein Transport</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Transfection</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuO1DAQtBCIHRa-AAn5xC3Z7sSTx4EDGgE70iIktJyt2O6wHiVxsJ1l5xv4Gn6Eb1oPGYkbp26pq6qruxh7jZAjYHV1yI_0oH1eAFQ5Yg4gnrANQgtZIYriKdsAoMhEU9QX7EUIBwBoGqyeswussSmgFBv269bNzgY3ku8C8f2eKzuZwO04Ox_txP_85mncOz8G3k2G08M6uNp9_YxcLZEbR4FPLvJwt8Q4EFcUfxJNPN4RnxY90LJS9TG6eejCyJPu7N1g-7Q1aX3nmoYhvGTP-m4I9OpcL9m3jx9ud9fZzZdP-937m0yX2zpmpe7LRpBQQB22paqoNahUq1JrWlHTFkFTXbQACo0pBfVKlL0WQndNj9vykr1ddZOHHwuFKEcbTg66idwSZNW0DbY1JmC5ArV3IXjq5ezt2PmjRJCnDORB_s1AnjKQiDJlkFhvzvKLGsn845yfngDvVgClI-8teRm0pUmTsZ50lMbZ_y54BORunUo</recordid><startdate>20070201</startdate><enddate>20070201</enddate><creator>Mirski, Shelagh E.L.</creator><creator>Sparks, Kathryn E.</creator><creator>Friedrich, Beate</creator><creator>Köhler, Matthias</creator><creator>Mo, Yin-Yuan</creator><creator>Beck, William T.</creator><creator>Cole, Susan P.C.</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20070201</creationdate><title>Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells</title><author>Mirski, Shelagh E.L. ; Sparks, Kathryn E. ; Friedrich, Beate ; Köhler, Matthias ; Mo, Yin-Yuan ; Beck, William T. ; Cole, Susan P.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-3cf384e4b0ea193b6e9d1bb9b3b6d947e510ce72900b1dd34efb43fc44ca8f153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>alpha Karyopherins - metabolism</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>CRM1</topic><topic>Cytoplasm - metabolism</topic><topic>DNA topoisomerase II</topic><topic>DNA Topoisomerases, Type II - metabolism</topic><topic>Exportin 1 Protein</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Importin α</topic><topic>Karyopherins - metabolism</topic><topic>Nuclear export</topic><topic>Nuclear import</topic><topic>Nuclear localization</topic><topic>Nucleocytoplasmic shuttling</topic><topic>Protein Isoforms</topic><topic>Protein Transport</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mirski, Shelagh E.L.</creatorcontrib><creatorcontrib>Sparks, Kathryn E.</creatorcontrib><creatorcontrib>Friedrich, Beate</creatorcontrib><creatorcontrib>Köhler, Matthias</creatorcontrib><creatorcontrib>Mo, Yin-Yuan</creatorcontrib><creatorcontrib>Beck, William T.</creatorcontrib><creatorcontrib>Cole, Susan P.C.</creatorcontrib><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>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mirski, Shelagh E.L.</au><au>Sparks, Kathryn E.</au><au>Friedrich, Beate</au><au>Köhler, Matthias</au><au>Mo, Yin-Yuan</au><au>Beck, William T.</au><au>Cole, Susan P.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2007-02-01</date><risdate>2007</risdate><volume>313</volume><issue>3</issue><spage>627</spage><epage>637</epage><pages>627-637</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Resistance to anticancer drugs that target DNA topoisomerase II (topo II) isoforms α and/or β is associated with decreased nuclear and increased cytoplasmic topo IIα. Earlier studies have confirmed that functional nuclear localization and export signal sequences (NLS and NES) are present in both isoforms. In this study, we show that topo II α and β bind and are imported into the nucleus by importin α1, α3, and α5 in conjunction with importin β. Topo IIα also binds exportin/CRM1 in vitro. However, wild-type topo IIα has only been observed in the cytoplasm of cells that are entering plateau phase growth. This suggests that topo IIα may shuttle between the nucleus and the cytoplasm with the equilibrium towards the nucleus in proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1 inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo IIα with a mutant NLS, suggesting that its export is being inhibited. However, homokaryon shuttling experiments indicate that fluorescence-tagged wild-type topo II α and β proteins do not shuttle in proliferating Cos-1 or HeLa cells. We conclude that topo II α and β nuclear export is inhibited in proliferating cells so that these proteins do not shuttle.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17182034</pmid><doi>10.1016/j.yexcr.2006.11.004</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-4827 |
| ispartof | Experimental cell research, 2007-02, Vol.313 (3), p.627-637 |
| issn | 0014-4827 1090-2422 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68981971 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | alpha Karyopherins - metabolism Animals Cell Line Cell Nucleus - metabolism Cell Proliferation Chlorocebus aethiops COS Cells CRM1 Cytoplasm - metabolism DNA topoisomerase II DNA Topoisomerases, Type II - metabolism Exportin 1 Protein HeLa Cells Humans Importin α Karyopherins - metabolism Nuclear export Nuclear import Nuclear localization Nucleocytoplasmic shuttling Protein Isoforms Protein Transport Receptors, Cytoplasmic and Nuclear - metabolism Transfection |
| title | Topoisomerase II binds importin α isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T15%3A23%3A26IST&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=Topoisomerase%20II%20binds%20importin%20%CE%B1%20isoforms%20and%20exportin/CRM1%20but%20does%20not%20shuttle%20between%20the%20nucleus%20and%20cytoplasm%20in%20proliferating%20cells&rft.jtitle=Experimental%20cell%20research&rft.au=Mirski,%20Shelagh%20E.L.&rft.date=2007-02-01&rft.volume=313&rft.issue=3&rft.spage=627&rft.epage=637&rft.pages=627-637&rft.issn=0014-4827&rft.eissn=1090-2422&rft_id=info:doi/10.1016/j.yexcr.2006.11.004&rft_dat=%3Cproquest_cross%3E68981971%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=68981971&rft_id=info:pmid/17182034&rft_els_id=S0014482706004629&rfr_iscdi=true |