Casein Kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in the cytoplasm
Identifieur interne : 006E25 ( Ncbi/Checkpoint ); précédent : 006E24; suivant : 006E26Casein Kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in the cytoplasm
Auteurs : Diana Golden ; Lloyd G. CantleySource :
- Oncogene [ 0950-9232 ] ; 2014.
Abstract
Nuclear Foxc2 is a transcriptional regulator of mesenchymal transformation during
developmental EMT and has been associated with EMT in malignant epithelia. Our laboratory
has shown that in normal epithelial cells Foxc2 is maintained in the cytoplasm where it
promotes an epithelial phenotype. The Foxc2 amino terminus has a consensus casein kinase 2
phosphorylation site at serine 124, and we now show that CK2 associates with Foxc2 and
phosphorylates this site
Url:
DOI: 10.1038/onc.2014.395
PubMed: 25486430
PubMed Central: 4459945
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Casein Kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in
the cytoplasm</title><author><name sortKey="Golden, Diana" sort="Golden, Diana" uniqKey="Golden D" first="Diana" last="Golden">Diana Golden</name><affiliation><nlm:aff id="A1">Center for Vascular Biology, University of Connecticut Health Center</nlm:aff><wicri:noCountry code="subfield">University of Connecticut Health Center</wicri:noCountry></affiliation></author><author><name sortKey="Cantley, Lloyd G" sort="Cantley, Lloyd G" uniqKey="Cantley L" first="Lloyd G." last="Cantley">Lloyd G. Cantley</name><affiliation><nlm:aff id="A2">Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine</nlm:aff><wicri:noCountry code="subfield">Yale University School of Medicine</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25486430</idno><idno type="pmc">4459945</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459945</idno><idno type="RBID">PMC:4459945</idno><idno type="doi">10.1038/onc.2014.395</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">004705</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004705</idno><idno type="wicri:Area/Pmc/Curation">004704</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004704</idno><idno type="wicri:Area/Pmc/Checkpoint">001C89</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001C89</idno><idno type="wicri:Area/Ncbi/Merge">006E25</idno><idno type="wicri:Area/Ncbi/Curation">006E25</idno><idno type="wicri:Area/Ncbi/Checkpoint">006E25</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Casein Kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in
the cytoplasm</title><author><name sortKey="Golden, Diana" sort="Golden, Diana" uniqKey="Golden D" first="Diana" last="Golden">Diana Golden</name><affiliation><nlm:aff id="A1">Center for Vascular Biology, University of Connecticut Health Center</nlm:aff><wicri:noCountry code="subfield">University of Connecticut Health Center</wicri:noCountry></affiliation></author><author><name sortKey="Cantley, Lloyd G" sort="Cantley, Lloyd G" uniqKey="Cantley L" first="Lloyd G." last="Cantley">Lloyd G. Cantley</name><affiliation><nlm:aff id="A2">Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine</nlm:aff><wicri:noCountry code="subfield">Yale University School of Medicine</wicri:noCountry></affiliation></author></analytic><series><title level="j">Oncogene</title><idno type="ISSN">0950-9232</idno><idno type="eISSN">1476-5594</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Nuclear Foxc2 is a transcriptional regulator of mesenchymal transformation during
developmental EMT and has been associated with EMT in malignant epithelia. Our laboratory
has shown that in normal epithelial cells Foxc2 is maintained in the cytoplasm where it
promotes an epithelial phenotype. The Foxc2 amino terminus has a consensus casein kinase 2
phosphorylation site at serine 124, and we now show that CK2 associates with Foxc2 and
phosphorylates this site <italic>in vitro</italic>. Knock-down or inhibition of the
CK2α/α′ kinase subunit in epithelial cells causes de novo
accumulation of Foxc2 in the nucleus. Mutation of serine 124 to leucine promotes
constitutive nuclear localization of Foxc2 and expression of mesenchymal genes, whereas an
S124D phosphomimetic leads to constitutive cytoplasmic localization and epithelial
maintenance. In malignant breast cancer cells the CK2β regulatory subunit is
downregulated and FOXC2 is found in the nucleus, correlating with an increase in
α-SMA expression. Restoration of CK2β expression in these cells results in
cytoplasmic localization of Foxc2, decreased α-SMA expression and reduced cell
migration and invasion. In contrast, knockdown of CK2β in normal breast epithelial
cells leads to FOXC2 nuclear localization, decreased E-cadherin expression, increased
α-SMA and vimentin expression, and enhanced cell migration and invasion. Based on
these findings we propose that Foxc2 is functionally maintained in the cytoplasm of normal
epithelial cells by CK2α/α′-mediated phosphorylation at serine 124
that is dependent on proper targeting of the holoenzyme via the CK2β regulatory
subunit.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wallin, A" uniqKey="Wallin A">A Wallin</name></author><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name></author><author><name sortKey="Jones, Tw" uniqKey="Jones T">TW Jones</name></author><author><name sortKey="Jaken, S" uniqKey="Jaken S">S Jaken</name></author><author><name sortKey="Stevens, Jl" uniqKey="Stevens J">JL Stevens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Witzgall, R" uniqKey="Witzgall R">R Witzgall</name></author><author><name sortKey="Brown, D" uniqKey="Brown D">D Brown</name></author><author><name sortKey="Schwarz, C" uniqKey="Schwarz C">C Schwarz</name></author><author><name sortKey="Bonventre, Jv" uniqKey="Bonventre J">JV Bonventre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Strutz, F" uniqKey="Strutz F">F Strutz</name></author><author><name sortKey="Okada, H" 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Ciais</name></author><author><name sortKey="Combes, F" uniqKey="Combes F">F Combes</name></author><author><name sortKey="Vandenbrouck, Y" uniqKey="Vandenbrouck Y">Y Vandenbrouck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tu, Yf" uniqKey="Tu Y">YF Tu</name></author><author><name sortKey="Kaipparettu, Ba" uniqKey="Kaipparettu B">BA Kaipparettu</name></author><author><name sortKey="Ma, Y" uniqKey="Ma Y">Y Ma</name></author><author><name sortKey="Wong, Lj" uniqKey="Wong L">LJ Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Jh" uniqKey="Lee J">JH Lee</name></author><author><name sortKey="Skalnik, Dg" uniqKey="Skalnik D">DG Skalnik</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Cantley, Lloyd G" sort="Cantley, Lloyd G" uniqKey="Cantley L" first="Lloyd G." last="Cantley">Lloyd G. Cantley</name><name sortKey="Golden, Diana" sort="Golden, Diana" uniqKey="Golden D" first="Diana" last="Golden">Diana Golden</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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