Induction of apoptosis by NORE1A in a manner dependent on its nuclear export
The RASSF family proteins were identified as tumor suppressors in a variety of human cancers, and evidenced distinct subcellular localization patterns among their subfamilies and isoforms. In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminu...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2008-03, Vol.368 (1), p.56-61 |
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| creator | Park, Sang-Joon Lee, Deresa Choi, Cheol-Yong Ryu, Si-Yun |
| description | The RASSF family proteins were identified as tumor suppressors in a variety of human cancers, and evidenced distinct subcellular localization patterns among their subfamilies and isoforms. In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminus (residues 372–379). Substitutions of three lysine residues of NORE1A NES to alanines (L372, 376, 379A) showed its localization to the dot structures of the nucleus, which was similar to the NORE1A localizations observed after the administration to cells of Leptomycin B, a nuclear export inhibitor. The NORE1A NES mutant inhibited caspase-mediated apoptosis, whereas wild-type NORE1A induced caspase-3 activation. Furthermore, the NORE1A NES mutant did not co-localize with GFP-MST1, the direct downstream target of NORE1A. These results show that the nuclear export of NORE1A via NES is involved in the NORE1A-mediated induction of apoptosis. |
| doi_str_mv | 10.1016/j.bbrc.2008.01.044 |
| format | Article |
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In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminus (residues 372–379). Substitutions of three lysine residues of NORE1A NES to alanines (L372, 376, 379A) showed its localization to the dot structures of the nucleus, which was similar to the NORE1A localizations observed after the administration to cells of Leptomycin B, a nuclear export inhibitor. The NORE1A NES mutant inhibited caspase-mediated apoptosis, whereas wild-type NORE1A induced caspase-3 activation. Furthermore, the NORE1A NES mutant did not co-localize with GFP-MST1, the direct downstream target of NORE1A. These results show that the nuclear export of NORE1A via NES is involved in the NORE1A-mediated induction of apoptosis.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2008.01.044</identifier><identifier>PMID: 18211824</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Active Transport, Cell Nucleus ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; ALANINES ; Animals ; APOPTOSIS ; Cell death signaling pathway ; Cell Line ; Cercopithecus aethiops ; Cytoplasm - metabolism ; Gene Deletion ; Humans ; LYSINE ; Mice ; Monomeric GTP-Binding Proteins - genetics ; Monomeric GTP-Binding Proteins - metabolism ; MST1 ; MUTANTS ; NEOPLASMS ; NITRIC OXIDE ; NORE1A ; Nuclear export signal ; Nuclear localization signal ; Nucleocytoplasmic shuttling ; PROTEINS</subject><ispartof>Biochemical and biophysical research communications, 2008-03, Vol.368 (1), p.56-61</ispartof><rights>2008 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-23801bae6be2ee0206e66b83280d10f07e21d94800821f864b17dec452fb77113</citedby><cites>FETCH-LOGICAL-c448t-23801bae6be2ee0206e66b83280d10f07e21d94800821f864b17dec452fb77113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2008.01.044$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18211824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21043671$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Sang-Joon</creatorcontrib><creatorcontrib>Lee, Deresa</creatorcontrib><creatorcontrib>Choi, Cheol-Yong</creatorcontrib><creatorcontrib>Ryu, Si-Yun</creatorcontrib><title>Induction of apoptosis by NORE1A in a manner dependent on its nuclear export</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The RASSF family proteins were identified as tumor suppressors in a variety of human cancers, and evidenced distinct subcellular localization patterns among their subfamilies and isoforms. In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminus (residues 372–379). Substitutions of three lysine residues of NORE1A NES to alanines (L372, 376, 379A) showed its localization to the dot structures of the nucleus, which was similar to the NORE1A localizations observed after the administration to cells of Leptomycin B, a nuclear export inhibitor. The NORE1A NES mutant inhibited caspase-mediated apoptosis, whereas wild-type NORE1A induced caspase-3 activation. Furthermore, the NORE1A NES mutant did not co-localize with GFP-MST1, the direct downstream target of NORE1A. These results show that the nuclear export of NORE1A via NES is involved in the NORE1A-mediated induction of apoptosis.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Active Transport, Cell Nucleus</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>ALANINES</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>Cell death signaling pathway</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>Cytoplasm - metabolism</subject><subject>Gene Deletion</subject><subject>Humans</subject><subject>LYSINE</subject><subject>Mice</subject><subject>Monomeric GTP-Binding Proteins - genetics</subject><subject>Monomeric GTP-Binding Proteins - metabolism</subject><subject>MST1</subject><subject>MUTANTS</subject><subject>NEOPLASMS</subject><subject>NITRIC OXIDE</subject><subject>NORE1A</subject><subject>Nuclear export signal</subject><subject>Nuclear localization signal</subject><subject>Nucleocytoplasmic shuttling</subject><subject>PROTEINS</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMGKFDEQhoMo7uzqC3iQgOCt26p0TPeAl2VZ3YXBBVHwFjpJNWaYSdokvbhvb5oZ8OahqMtXP399jL1BaBFQfdi3xiTbCoChBWxBymdsg7CFRiDI52wDAKoRW_x5wS5z3gMgSrV9yS5wEFhHbtjuPrjFFh8DjxMf5ziXmH3m5ol_ffh2i9fcBz7y4xgCJe5opuAoFF55XzIPiz3QmDj9mWMqr9iLaTxken3eV-zH59vvN3fN7uHL_c31rrFSDqUR3QBoRlKGBBEIUKSUGToxgEOYoCeBbiuH-pfAaVDSYO_Iyo9iMn2P2F2xd6fcmIvX2fpC9peNtaItev29U_1KvT9Rc4q_F8pFH322dDiMgeKSdQ9dtdjLCooTaFPMOdGk5-SPY3rSCHo1rfd6Na1X0xpQV9P16O05fTFHcv9Ozmor8OkEUDXx6CmtRSlYcj6tPV30_8v_Cw5IjKA</recordid><startdate>20080328</startdate><enddate>20080328</enddate><creator>Park, Sang-Joon</creator><creator>Lee, Deresa</creator><creator>Choi, Cheol-Yong</creator><creator>Ryu, Si-Yun</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><scope>OTOTI</scope></search><sort><creationdate>20080328</creationdate><title>Induction of apoptosis by NORE1A in a manner dependent on its nuclear export</title><author>Park, Sang-Joon ; Lee, Deresa ; Choi, Cheol-Yong ; Ryu, Si-Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-23801bae6be2ee0206e66b83280d10f07e21d94800821f864b17dec452fb77113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Active Transport, Cell Nucleus</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>ALANINES</topic><topic>Animals</topic><topic>APOPTOSIS</topic><topic>Cell death signaling pathway</topic><topic>Cell Line</topic><topic>Cercopithecus aethiops</topic><topic>Cytoplasm - metabolism</topic><topic>Gene Deletion</topic><topic>Humans</topic><topic>LYSINE</topic><topic>Mice</topic><topic>Monomeric GTP-Binding Proteins - genetics</topic><topic>Monomeric GTP-Binding Proteins - metabolism</topic><topic>MST1</topic><topic>MUTANTS</topic><topic>NEOPLASMS</topic><topic>NITRIC OXIDE</topic><topic>NORE1A</topic><topic>Nuclear export signal</topic><topic>Nuclear localization signal</topic><topic>Nucleocytoplasmic shuttling</topic><topic>PROTEINS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Sang-Joon</creatorcontrib><creatorcontrib>Lee, Deresa</creatorcontrib><creatorcontrib>Choi, Cheol-Yong</creatorcontrib><creatorcontrib>Ryu, Si-Yun</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><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Sang-Joon</au><au>Lee, Deresa</au><au>Choi, Cheol-Yong</au><au>Ryu, Si-Yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of apoptosis by NORE1A in a manner dependent on its nuclear export</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2008-03-28</date><risdate>2008</risdate><volume>368</volume><issue>1</issue><spage>56</spage><epage>61</epage><pages>56-61</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The RASSF family proteins were identified as tumor suppressors in a variety of human cancers, and evidenced distinct subcellular localization patterns among their subfamilies and isoforms. In this study, we showed that NORE1A was exported actively via its nuclear export signal (NES) in the C-terminus (residues 372–379). Substitutions of three lysine residues of NORE1A NES to alanines (L372, 376, 379A) showed its localization to the dot structures of the nucleus, which was similar to the NORE1A localizations observed after the administration to cells of Leptomycin B, a nuclear export inhibitor. The NORE1A NES mutant inhibited caspase-mediated apoptosis, whereas wild-type NORE1A induced caspase-3 activation. Furthermore, the NORE1A NES mutant did not co-localize with GFP-MST1, the direct downstream target of NORE1A. These results show that the nuclear export of NORE1A via NES is involved in the NORE1A-mediated induction of apoptosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18211824</pmid><doi>10.1016/j.bbrc.2008.01.044</doi><tpages>6</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Active Transport, Cell Nucleus Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism ALANINES Animals APOPTOSIS Cell death signaling pathway Cell Line Cercopithecus aethiops Cytoplasm - metabolism Gene Deletion Humans LYSINE Mice Monomeric GTP-Binding Proteins - genetics Monomeric GTP-Binding Proteins - metabolism MST1 MUTANTS NEOPLASMS NITRIC OXIDE NORE1A Nuclear export signal Nuclear localization signal Nucleocytoplasmic shuttling PROTEINS |
| title | Induction of apoptosis by NORE1A in a manner dependent on its nuclear export |
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