Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression*
Identifieur interne : 000036 ( Pmc/Curation ); précédent : 000035; suivant : 000037Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression*
Auteurs : Trevor M. Morey [Canada] ; Rabih Roufayel [Canada] ; Donald S. Johnston [Canada] ; Andrew S. Fletcher [Canada] ; Dick D. Mosser [Canada]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2015.
Abstract
Url:
DOI: 10.1074/jbc.M114.625988
PubMed: 25829494
PubMed Central: 4416849
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Morey, Trevor M" sort="Morey, Trevor M" uniqKey="Morey T" first="Trevor M." last="Morey">Trevor M. Morey</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Roufayel, Rabih" sort="Roufayel, Rabih" uniqKey="Roufayel R" first="Rabih" last="Roufayel">Rabih Roufayel</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Johnston, Donald S" sort="Johnston, Donald S" uniqKey="Johnston D" first="Donald S." last="Johnston">Donald S. Johnston</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Fletcher, Andrew S" sort="Fletcher, Andrew S" uniqKey="Fletcher A" first="Andrew S." last="Fletcher">Andrew S. Fletcher</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Mosser, Dick D" sort="Mosser, Dick D" uniqKey="Mosser D" first="Dick D." last="Mosser">Dick D. Mosser</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25829494</idno><idno type="pmc">4416849</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416849</idno><idno type="RBID">PMC:4416849</idno><idno type="doi">10.1074/jbc.M114.625988</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000036</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000036</idno><idno type="wicri:Area/Pmc/Curation">000036</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000036</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Morey, Trevor M" sort="Morey, Trevor M" uniqKey="Morey T" first="Trevor M." last="Morey">Trevor M. Morey</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Roufayel, Rabih" sort="Roufayel, Rabih" uniqKey="Roufayel R" first="Rabih" last="Roufayel">Rabih Roufayel</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Johnston, Donald S" sort="Johnston, Donald S" uniqKey="Johnston D" first="Donald S." last="Johnston">Donald S. Johnston</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Fletcher, Andrew S" sort="Fletcher, Andrew S" uniqKey="Fletcher A" first="Andrew S." last="Fletcher">Andrew S. Fletcher</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author><author><name sortKey="Mosser, Dick D" sort="Mosser, Dick D" uniqKey="Mosser D" first="Dick D." last="Mosser">Dick D. Mosser</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> HSP70 inhibits heat-induced apoptosis by preventing NOXA accumulation.</p><p><bold>Results:</bold> Inhibition of CDK5 in heat-shocked cells reduces levels of miR-23a leading to increased NOXA abundance, which is prevented by HSP70.</p><p><bold>Conclusion:</bold> CDK5 regulates miR-23a expression and affects NOXA abundance.</p><p><bold>Significance:</bold> The prosurvival function of HSP70 can be attributed to its ability to prevent the stress-induced inhibition of CDK5.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>11200 Rockville Pike, Suite 302, Rockville, MD 20852-3110, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25829494</article-id><article-id pub-id-type="pmc">4416849</article-id><article-id pub-id-type="publisher-id">M114.625988</article-id><article-id pub-id-type="doi">10.1074/jbc.M114.625988</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cell Biology</subject></subj-group></article-categories><title-group><article-title>Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">CDK5 Regulation of NOXA Expression</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Morey</surname><given-names>Trevor M.</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Roufayel</surname><given-names>Rabih</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Johnston</surname><given-names>Donald S.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Fletcher</surname><given-names>Andrew S.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Mosser</surname><given-names>Dick D.</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed: <addr-line>Dept. of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.</addr-line> Tel.: <phone>519-824-4120 ext. 58059</phone>; Fax: <fax>519-837-1802</fax>; E-mail: <email>rmosser@uoguelph.ca</email>.</corresp><fn fn-type="equal" id="FN2"><label>1</label><p>These authors contributed equally to the work.</p></fn></author-notes><pub-date pub-type="ppub"><day>1</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>31</day><month>3</month><year>2015</year></pub-date><volume>290</volume><issue>18</issue><fpage>11443</fpage><lpage>11454</lpage><history><date date-type="received"><day>13</day><month>11</month><year>2014</year></date><date date-type="rev-recd"><day>31</day><month>3</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01815011443.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> HSP70 inhibits heat-induced apoptosis by preventing NOXA accumulation.</p><p><bold>Results:</bold> Inhibition of CDK5 in heat-shocked cells reduces levels of miR-23a leading to increased NOXA abundance, which is prevented by HSP70.</p><p><bold>Conclusion:</bold> CDK5 regulates miR-23a expression and affects NOXA abundance.</p><p><bold>Significance:</bold> The prosurvival function of HSP70 can be attributed to its ability to prevent the stress-induced inhibition of CDK5.</p></abstract><abstract><p>Hyperthermia is a proteotoxic stress that is lethal when exposure is extreme but also cytoprotective in that sublethal exposure leads to the synthesis of heat shock proteins, including HSP70, which are able to inhibit stress-induced apoptosis. CDK5 is an atypical cyclin-dependent kinase family member that regulates many cellular functions including motility and survival. Here we show that exposure of a human lymphoid cell line to hyperthermia causes CDK5 insolubilization and loss of tyrosine-15 phosphorylation, both of which were prevented in cells overexpressing HSP70. Inhibition of CDK5 activity with roscovitine-sensitized cells to heat induced apoptosis indicating a protective role for CDK5 in inhibiting heat-induced apoptosis. Both roscovitine and heat shock treatment caused increased accumulation of NOXA a pro-apoptotic BH3-only member of the BCL2 family. The increased abundance of NOXA by CDK5 inhibition was not a result of changes in NOXA protein turnover. Instead, CDK5 inhibition increased NOXA mRNA and protein levels by decreasing the expression of miR-23a, whereas overexpressing the CDK5 activator p35 attenuated both of these effects on NOXA and miR-23a expression. Lastly, overexpression of miR-23a prevented apoptosis under conditions in which CDK5 activity was inhibited. These results demonstrate that CDK5 activity provides resistance to heat-induced apoptosis through the expression of miR-23a and subsequent suppression of NOXA synthesis. Additionally, they indicate that hyperthermia induces apoptosis through the insolubilization and inhibition of CDK5 activity.</p></abstract><kwd-group><kwd>70 kilodalton heat shock protein (Hsp70)</kwd><kwd>apoptosis</kwd><kwd>cyclin-dependent kinase (CDK)</kwd><kwd>heat shock protein (HSP)</kwd><kwd>hyperthermia</kwd><kwd>microRNA (miRNA)</kwd><kwd>CDK5</kwd><kwd>miR-23a</kwd><kwd>noxa</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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