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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stress-induced decrease in TRAF2 stability is mediated by Siah2</title>
<author><name sortKey="Habelhah, Hasem" sort="Habelhah, Hasem" uniqKey="Habelhah H" first="Hasem" last="Habelhah">Hasem Habelhah</name>
</author>
<author><name sortKey="Frew, Ian J" sort="Frew, Ian J" uniqKey="Frew I" first="Ian J." last="Frew">Ian J. Frew</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laine, Aaron" sort="Laine, Aaron" uniqKey="Laine A" first="Aaron" last="Laine">Aaron Laine</name>
</author>
<author><name sortKey="Janes, Peter W" sort="Janes, Peter W" uniqKey="Janes P" first="Peter W." last="Janes">Peter W. Janes</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Relaix, Frederic" sort="Relaix, Frederic" uniqKey="Relaix F" first="Frederic" last="Relaix">Frederic Relaix</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sassoon, David" sort="Sassoon, David" uniqKey="Sassoon D" first="David" last="Sassoon">David Sassoon</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bowtell, David D L" sort="Bowtell, David D L" uniqKey="Bowtell D" first="David D. L." last="Bowtell">David D. L. Bowtell</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ronai, Ze V" sort="Ronai, Ze V" uniqKey="Ronai Z" first="Ze V" last="Ronai">Ze V Ronai</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">12411493</idno>
<idno type="pmc">131073</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC131073</idno>
<idno type="RBID">PMC:131073</idno>
<idno type="doi">10.1093/emboj/cdf576</idno>
<date when="2002">2002</date>
<idno type="wicri:Area/Pmc/Corpus">000F75</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F75</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Stress-induced decrease in TRAF2 stability is mediated by Siah2</title>
<author><name sortKey="Habelhah, Hasem" sort="Habelhah, Hasem" uniqKey="Habelhah H" first="Hasem" last="Habelhah">Hasem Habelhah</name>
</author>
<author><name sortKey="Frew, Ian J" sort="Frew, Ian J" uniqKey="Frew I" first="Ian J." last="Frew">Ian J. Frew</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Laine, Aaron" sort="Laine, Aaron" uniqKey="Laine A" first="Aaron" last="Laine">Aaron Laine</name>
</author>
<author><name sortKey="Janes, Peter W" sort="Janes, Peter W" uniqKey="Janes P" first="Peter W." last="Janes">Peter W. Janes</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Relaix, Frederic" sort="Relaix, Frederic" uniqKey="Relaix F" first="Frederic" last="Relaix">Frederic Relaix</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sassoon, David" sort="Sassoon, David" uniqKey="Sassoon D" first="David" last="Sassoon">David Sassoon</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bowtell, David D L" sort="Bowtell, David D L" uniqKey="Bowtell D" first="David D. L." last="Bowtell">David D. L. Bowtell</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ronai, Ze V" sort="Ronai, Ze V" uniqKey="Ronai Z" first="Ze V" last="Ronai">Ze V Ronai</name>
<affiliation><nlm:aff id="N0x9a7ddc8.0x998b8c0"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The EMBO Journal</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
<imprint><date when="2002">2002</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>TRAF2 serves as a central regulator of the cellular response to stress and cytokines through the regulation of key stress-signaling cascades. Here we demonstrate that wild-type, but not RING mutant, Siah2 targets TRAF2 for ubiquitylation and degradation <italic>in vitro</italic>
. Siah2 mediates equally efficient ubiquitylation of RING mutant TRAF2. <italic>In vivo</italic>
, Siah2 primarily targets TRAF2 for degradation under stress conditions. Tumor necrosis factor-α (TNF-α) and actinomycin D treatment results in accelerated TRAF2 degradation in wild-type mouse embryo fibroblasts (MEFs), as compared with <italic>Siah2</italic>
<sup>–/–</sup>
cells. Similarly, TRAF2 half-life is prolonged in <italic>Siah2</italic>
<sup>–/–</sup>
compared with wild-type MEFs subjected to stress stimuli. Siah2 efficiently decreases TNF-α-dependent induction of JNK activity and transcriptional activation of NF-κB. Apoptosis induced by TNF-α and actinomycin D treatment is increased upon expression of Siah2, or attenuated upon expression of TRAF2 or RING mutant Siah2. Identifying Siah2 as a regulator of TRAF2 stability reveals its role in the regulation of TRAF2 signaling following exposure to stress.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">EMBO J</journal-id>
<journal-title>The EMBO Journal</journal-title>
<issn pub-type="ppub">0261-4189</issn>
<issn pub-type="epub">1460-2075</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">12411493</article-id>
<article-id pub-id-type="pmc">131073</article-id>
<article-id pub-id-type="publisher-id">cdf576</article-id>
<article-id pub-id-type="doi">10.1093/emboj/cdf576</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Stress-induced decrease in TRAF2 stability is mediated by Siah2</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Habelhah</surname>
<given-names>Hasem</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Frew</surname>
<given-names>Ian J.</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Laine</surname>
<given-names>Aaron</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Janes</surname>
<given-names>Peter W.</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Relaix</surname>
<given-names>Frederic</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sassoon</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bowtell</surname>
<given-names>David D.L.</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ronai</surname>
<given-names>Ze’ev</given-names>
</name>
<xref ref-type="aff" rid="N0x9a7ddc8.0x998b8c0">4</xref>
</contrib>
</contrib-group>
<aff id="N0x9a7ddc8.0x998b8c0">Ruttenberg Cancer Center and<label>3</label>
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA,<label>1</label>
Peter MacCallum Cancer Institute, Melbourne 3002, Victoria, Australia and<label>2</label>
Department of Molecular Biology, Institute Pasteur, 75724 Paris, France<label>4</label>
Corresponding author e-mail:<email>zeev.ronai@mssm.edu</email>
</aff>
<pub-date pub-type="ppub"><day>1</day>
<month>11</month>
<year>2002</year>
</pub-date>
<volume>21</volume>
<issue>21</issue>
<fpage>5756</fpage>
<lpage>5765</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.emboj.oupjournals.org/content/vol21/issue21/"></ext-link>
<history><date date-type="received"><day>7</day>
<month>6</month>
<year>2002</year>
</date>
<date date-type="rev-recd"><day>21</day>
<month>8</month>
<year>2002</year>
</date>
<date date-type="accepted"><day>10</day>
<month>9</month>
<year>2002</year>
</date>
</history>
<copyright-statement>Copyright © 2002 European Molecular Biology Organization</copyright-statement>
<copyright-year>2002</copyright-year>
<abstract><p>TRAF2 serves as a central regulator of the cellular response to stress and cytokines through the regulation of key stress-signaling cascades. Here we demonstrate that wild-type, but not RING mutant, Siah2 targets TRAF2 for ubiquitylation and degradation <italic>in vitro</italic>
. Siah2 mediates equally efficient ubiquitylation of RING mutant TRAF2. <italic>In vivo</italic>
, Siah2 primarily targets TRAF2 for degradation under stress conditions. Tumor necrosis factor-α (TNF-α) and actinomycin D treatment results in accelerated TRAF2 degradation in wild-type mouse embryo fibroblasts (MEFs), as compared with <italic>Siah2</italic>
<sup>–/–</sup>
cells. Similarly, TRAF2 half-life is prolonged in <italic>Siah2</italic>
<sup>–/–</sup>
compared with wild-type MEFs subjected to stress stimuli. Siah2 efficiently decreases TNF-α-dependent induction of JNK activity and transcriptional activation of NF-κB. Apoptosis induced by TNF-α and actinomycin D treatment is increased upon expression of Siah2, or attenuated upon expression of TRAF2 or RING mutant Siah2. Identifying Siah2 as a regulator of TRAF2 stability reveals its role in the regulation of TRAF2 signaling following exposure to stress.</p>
</abstract>
<kwd-group><kwd>JNK/NF-κB/Siah2/stress/TRAF2</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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