Mitotic Phosphorylation of Cdc25B Ser321 Disrupts 14-3-3 Binding to the High Affinity Ser323 Site*
Identifieur interne : 001772 ( Pmc/Curation ); précédent : 001771; suivant : 001773Mitotic Phosphorylation of Cdc25B Ser321 Disrupts 14-3-3 Binding to the High Affinity Ser323 Site*
Auteurs : Puji Astuti ; Rose Boutros ; Bernard Ducommun [France] ; Brian GabrielliSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2010.
Abstract
Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser323 being the highest affinity binding and is highly homologous to the Ser216 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser323 increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser323 phosphorylation is maintained into mitosis, but phosphorylation of Ser321 disrupts 14-3-3 binding to Ser323, mimicking the effect of inhibiting Ser323 phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser321 appears to have a role in stabilizing 14-3-3 binding to Ser323, and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser323. Ser321 is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser321 acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser323 and enhancing the dephosphorylation of Ser323 to block 14-3-3 binding to this site.
Url:
DOI: 10.1074/jbc.M110.138412
PubMed: 20801879
PubMed Central: 2966050
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mitotic Phosphorylation of Cdc25B Ser<sup>321</sup> Disrupts 14-3-3 Binding to the High Affinity Ser<sup>323</sup> Site<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Astuti, Puji" sort="Astuti, Puji" uniqKey="Astuti P" first="Puji" last="Astuti">Puji Astuti</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Boutros, Rose" sort="Boutros, Rose" uniqKey="Boutros R" first="Rose" last="Boutros">Rose Boutros</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Ducommun, Bernard" sort="Ducommun, Bernard" uniqKey="Ducommun B" first="Bernard" last="Ducommun">Bernard Ducommun</name><affiliation wicri:level="1"><nlm:aff id="aff2">LBCMCP, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse, France,</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LBCMCP, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">LBCMCP-UMR5088, CNRS, F-31062 Toulouse, France,</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LBCMCP-UMR5088, CNRS, F-31062 Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff wicri:cut=", and" id="aff4">CHU Purpan, TSA 40031, F-31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Purpan, TSA 40031, F-31059 Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Gabrielli, Brian" sort="Gabrielli, Brian" uniqKey="Gabrielli B" first="Brian" last="Gabrielli">Brian Gabrielli</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20801879</idno><idno type="pmc">2966050</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966050</idno><idno type="RBID">PMC:2966050</idno><idno type="doi">10.1074/jbc.M110.138412</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001913</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001913</idno><idno type="wicri:Area/Pmc/Curation">001772</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001772</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mitotic Phosphorylation of Cdc25B Ser<sup>321</sup> Disrupts 14-3-3 Binding to the High Affinity Ser<sup>323</sup> Site<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Astuti, Puji" sort="Astuti, Puji" uniqKey="Astuti P" first="Puji" last="Astuti">Puji Astuti</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Boutros, Rose" sort="Boutros, Rose" uniqKey="Boutros R" first="Rose" last="Boutros">Rose Boutros</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Ducommun, Bernard" sort="Ducommun, Bernard" uniqKey="Ducommun B" first="Bernard" last="Ducommun">Bernard Ducommun</name><affiliation wicri:level="1"><nlm:aff id="aff2">LBCMCP, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse, France,</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LBCMCP, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">LBCMCP-UMR5088, CNRS, F-31062 Toulouse, France,</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LBCMCP-UMR5088, CNRS, F-31062 Toulouse</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff wicri:cut=", and" id="aff4">CHU Purpan, TSA 40031, F-31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Purpan, TSA 40031, F-31059 Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Gabrielli, Brian" sort="Gabrielli, Brian" uniqKey="Gabrielli B" first="Brian" last="Gabrielli">Brian Gabrielli</name><affiliation><nlm:aff id="aff1"></nlm:aff></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="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser<sup>323</sup> being the highest affinity binding and is highly homologous to the Ser<sup>216</sup> 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser<sup>323</sup> increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser<sup>323</sup> phosphorylation is maintained into mitosis, but phosphorylation of Ser<sup>321</sup> disrupts 14-3-3 binding to Ser<sup>323</sup>, mimicking the effect of inhibiting Ser<sup>323</sup> phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser<sup>321</sup> appears to have a role in stabilizing 14-3-3 binding to Ser<sup>323</sup>, and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser<sup>323</sup>. Ser<sup>321</sup> is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser<sup>321</sup> acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser<sup>323</sup> and enhancing the dephosphorylation of Ser<sup>323</sup> to block 14-3-3 binding to this site.</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="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>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20801879</article-id><article-id pub-id-type="pmc">2966050</article-id><article-id pub-id-type="publisher-id">M110.138412</article-id><article-id pub-id-type="doi">10.1074/jbc.M110.138412</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cell Biology</subject></subj-group></article-categories><title-group><article-title>Mitotic Phosphorylation of Cdc25B Ser<sup>321</sup> Disrupts 14-3-3 Binding to the High Affinity Ser<sup>323</sup> Site<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">Disruption of 14-3-3 Binding to Cdc25B</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Astuti</surname><given-names>Puji</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boutros</surname><given-names>Rose</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff5"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ducommun</surname><given-names>Bernard</given-names></name><xref ref-type="aff" rid="aff2"><sup>¶</sup></xref><xref ref-type="aff" rid="aff3"><sup>‖</sup></xref><xref ref-type="aff" rid="aff4">**</xref></contrib><contrib contrib-type="author"><name><surname>Gabrielli</surname><given-names>Brian</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia,</aff><aff id="aff2"><label>¶</label>LBCMCP, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse, France,</aff><aff id="aff3"><label>‖</label>LBCMCP-UMR5088, CNRS, F-31062 Toulouse, France,</aff><aff id="aff4"><label>**</label>CHU Purpan, TSA 40031, F-31059 Toulouse, France, and</aff><aff id="aff5">the<label>§</label>Children's Medical Research Institute, Westmead, New South Wales 2145, Australia</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> NHMRC Senior Research Fellow. To whom correspondence should be addressed. Fax: <fax>61-7-3240-7129</fax>; E-mail: <email>brianG@uq.edu.au</email>.</corresp><fn fn-type="supported-by" id="FN2"><label>1</label><p>Supported by a scholarship from AusAID. Present address: Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia.</p></fn></author-notes><pub-date pub-type="ppub"><day>5</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>27</day><month>8</month><year>2010</year></pub-date><volume>285</volume><issue>45</issue><fpage>34364</fpage><lpage>34370</lpage><history><date date-type="received"><day>27</day><month>4</month><year>2010</year></date><date date-type="rev-recd"><day>17</day><month>8</month><year>2010</year></date></history><permissions><copyright-statement>© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc04510034364.pdf"></self-uri><abstract><p>Cdc25B is a key regulator of entry into mitosis, and its activity and localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3 binding sites on Cdc25B, with Ser<sup>323</sup> being the highest affinity binding and is highly homologous to the Ser<sup>216</sup> 14-3-3 binding site on Cdc25C. Loss of 14-3-3 binding to Ser<sup>323</sup> increases cyclin/Cdk substrate access to the catalytic site, thereby increasing its activity. It also affects the localization of Cdc25B. Thus, phosphorylation and 14-3-3 binding to this site is essential for down-regulating Cdc25B activity, blocking its mitosis promoting function. The question of how this inhibitory signal is relieved to allow Cdc25B activation and entry into mitosis is yet to be resolved. Here, we show that Ser<sup>323</sup> phosphorylation is maintained into mitosis, but phosphorylation of Ser<sup>321</sup> disrupts 14-3-3 binding to Ser<sup>323</sup>, mimicking the effect of inhibiting Ser<sup>323</sup> phosphorylation on both Cdc25B activity and localization. The unphosphorylated Ser<sup>321</sup> appears to have a role in stabilizing 14-3-3 binding to Ser<sup>323</sup>, and loss of the Ser hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A consequence of loss of 14-3-3 binding is dephosphorylation of Ser<sup>323</sup>. Ser<sup>321</sup> is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser<sup>321</sup> acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to Ser<sup>323</sup> and enhancing the dephosphorylation of Ser<sup>323</sup> to block 14-3-3 binding to this site.</p></abstract><kwd-group><kwd>CDK (Cyclin-dependent Kinase)</kwd><kwd>Cell Cycle</kwd><kwd>Dual Specificity Phosphoprotein Phosphatase</kwd><kwd>Mitosis</kwd><kwd>Site-directed Mutagenesis</kwd><kwd>14-3-3</kwd><kwd>Cdc25B</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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