Stability of nucleolar versus non-nucleolar forms of human p14ARF
Fusion proteins containing the amino-terminal domain of human p14 ARF linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic...
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Veröffentlicht in: | Oncogene 2004-08, Vol.23 (37), p.6186-6192 |
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creator | Rodway, Helen Llanos, Susana Rowe, Janice Peters, Gordon |
description | Fusion proteins containing the amino-terminal domain of human p14
ARF
linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF. |
doi_str_mv | 10.1038/sj.onc.1207854 |
format | Article |
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ARF
linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1207854</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Antigens ; Apoptosis ; Biological and medical sciences ; Cell Biology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Fundamental and applied biological sciences. Psychology ; Green fluorescent protein ; Human Genetics ; Internal Medicine ; Localization ; MDM2 protein ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Nucleoli ; Oncology ; original-paper ; p53 Protein ; Proteasomes ; Proteins</subject><ispartof>Oncogene, 2004-08, Vol.23 (37), p.6186-6192</ispartof><rights>Springer Nature Limited 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 19, 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2884-924acc64c0b47037896506db489df50bd2568c468d304cab52da9884e56db2843</citedby><cites>FETCH-LOGICAL-c2884-924acc64c0b47037896506db489df50bd2568c468d304cab52da9884e56db2843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1207854$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1207854$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16036756$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodway, Helen</creatorcontrib><creatorcontrib>Llanos, Susana</creatorcontrib><creatorcontrib>Rowe, Janice</creatorcontrib><creatorcontrib>Peters, Gordon</creatorcontrib><title>Stability of nucleolar versus non-nucleolar forms of human p14ARF</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>Fusion proteins containing the amino-terminal domain of human p14
ARF
linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF.</description><subject>Antigens</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Green fluorescent protein</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Localization</subject><subject>MDM2 protein</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Nucleoli</subject><subject>Oncology</subject><subject>original-paper</subject><subject>p53 Protein</subject><subject>Proteasomes</subject><subject>Proteins</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kEtLLDEQhYMoOD62rpsrLnusJJV0shzEFwiCj3VIp9PaQ08yN5kW_PdGZmBWUouCqu_UKQ4hFxTmFLi6zst5DG5OGTRK4AGZUWxkLYTGQzIDLaDWjLNjcpLzEgAaDWxGFq8b2w7jsPmuYl-FyY0-jjZVXz7lKVchhno_7GNa5V_uc1rZUK0pLl7uzshRb8fsz3f9lLzf3b7dPNRPz_ePN4un2jGlsHijdU6igxYb4I3SUoDsWlS66wW0HRNSOZSq44DOtoJ1VhehFwViCvkpudzeXaf4f_J5Y5ZxSqFYGiaRct5wJQr170-KNRwVUF2g-Rb6sKM3Q-jjJllXqvOrwcXg-6HMF1RpypEj7gUuxZyT7806DSubvg0F8xu-yUtTwje78IvgaveGzc6OfbLBDXmvksBlI2ThrrdcLqvw4dP-3T8u_wCrZZIS</recordid><startdate>20040819</startdate><enddate>20040819</enddate><creator>Rodway, Helen</creator><creator>Llanos, Susana</creator><creator>Rowe, Janice</creator><creator>Peters, Gordon</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20040819</creationdate><title>Stability of nucleolar versus non-nucleolar forms of human p14ARF</title><author>Rodway, Helen ; Llanos, Susana ; Rowe, Janice ; Peters, Gordon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2884-924acc64c0b47037896506db489df50bd2568c468d304cab52da9884e56db2843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antigens</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Green fluorescent protein</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Localization</topic><topic>MDM2 protein</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Nucleoli</topic><topic>Oncology</topic><topic>original-paper</topic><topic>p53 Protein</topic><topic>Proteasomes</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodway, Helen</creatorcontrib><creatorcontrib>Llanos, Susana</creatorcontrib><creatorcontrib>Rowe, Janice</creatorcontrib><creatorcontrib>Peters, Gordon</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodway, Helen</au><au>Llanos, Susana</au><au>Rowe, Janice</au><au>Peters, Gordon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stability of nucleolar versus non-nucleolar forms of human p14ARF</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><date>2004-08-19</date><risdate>2004</risdate><volume>23</volume><issue>37</issue><spage>6186</spage><epage>6192</epage><pages>6186-6192</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Fusion proteins containing the amino-terminal domain of human p14
ARF
linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><doi>10.1038/sj.onc.1207854</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antigens Apoptosis Biological and medical sciences Cell Biology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Fundamental and applied biological sciences. Psychology Green fluorescent protein Human Genetics Internal Medicine Localization MDM2 protein Medicine Medicine & Public Health Molecular and cellular biology Nucleoli Oncology original-paper p53 Protein Proteasomes Proteins |
title | Stability of nucleolar versus non-nucleolar forms of human p14ARF |
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