14-3-3 Binding Sites in the Snail Protein Are Essential for Snail-Mediated Transcriptional Repression and Epithelial-Mesenchymal Differentiation

Article Article scientifique Article 14-3-3 Binding Sites in the Snail Protein Are Essential for Snail-Mediated Transcriptional Repression and Epithelial-Mesenchymal Differentiation eng 2010-06-01 2010-06-01 author Hou Zhaoyuan author Peng Hongzhuang author White David E. author Wang Pu 104032 author Lieberman Paul M. author Halazonetis Thanos 0000-0001-8384-5030 641033 Département de biologie moléculaire et cellulaire (MOCEL) author Rauscher Frank J. 4385-4393 10.1158/0008-5472.CAN-10-0070 20501852 0008-5472 PMC2894621 https://aacrjournals.org/cancerres/article/70/11/4385/559422/14-3-3-Binding-Sites-in-the-Snail-Protein-Are <p>The Snail transcription factor is a repressor and a master regulator of epithelial-mesenchymal transition (EMT) events in normal embryonic development and during tumor metastases. Snail directly regulates genes affecting cell adhesion, motility, and polarity. Invasive tumor cells express high levels of Snail, which is a marker for aggressive disease and poor prognosis. Transcriptional repression and EMT induction by Snail requires binding to its obligate corepressor, the LIM protein Ajuba. It is unclear how this complex is assembled and maintained on Snail target genes. Here we define functional 14-3-3 binding motifs in Snail and Ajuba, which selectively bind 14-3-3 protein isoforms. In Snail, an NH2-terminal motif in the repression domain cooperates with a COOH-terminal, high-affinity motif for binding to 14-3-3 proteins. Coordinate mutation of both motifs abolishes 14-3-3 binding and inhibits Snail-mediated gene repression and EMT differentiation. Snail, 14-3-3 proteins, and Ajuba form a ternary complex that is readily detected through chromatin immunoprecipitation at the endogenous E-cadherin promoter. Collectively, these data show that 14-3-3 proteins are new components of the Snail transcriptional repression machinery and mediate its important biological functions.</p> Dewey 570 NCI NIH HHS P30 CA010815 43 Département de biologie moléculaire 161 false 811 Groupe Halazonetis Cancer research 70 11 5bb18fbe-22d7-4751-ba64-b0b1a2f5bb31 Article (Published version) Restricted Article-scientifique-from-crossref.pdf 472552 application/pdf 1a72f1e2d8ad0339881a35ecca81b977d575e922fb7d2cff6f60ca570d367001 restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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14-3-3 Binding Sites in the Snail Protein Are Essential for Snail-Mediated Transcriptional Repression and Epithelial-Mesenchymal Differentiation	Cancer research			2010	77	0

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