title: Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
abstract: Snail1 and Snail2, two highly related members of the Snail superfamily, are direct transcriptional repressors of E-cadherin and EMT inducers. Previous comparative gene profiling analyses have revealed important differences in the gene expression pattern regulated by Snail1 and Snail2, indicating functional differences between both factors. The molecular mechanism of Snail1-mediated repression has been elucidated to some extent, but very little is presently known on the repression mediated by Snail2. In the present work, we report on the characterization of Snail2 repression of E-cadherin and its regulation by phosphorylation. Both the N-terminal SNAG and the central SLUG domains of Snail2 are required for efficient repression of the E-cadherin promoter. The co-repressor NCoR interacts with Snail2 through the SNAG domain, while CtBP1 is recruited through the SLUG domain. Interestingly, the SNAG domain is absolutely required for EMT induction while the SLUG domain plays a negative modulation of Snail2 mediated EMT. Additionally, we identify here novel in vivo phosphorylation sites at serine 4 and serine 88 of Snail2 and demonstrate the functional implication of serine 4 in the regulation of Snail2-mediated repressor activity of E-cadherin and in Snail2 induction of EMT.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Autonoma de Madrid (UAM), Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, IdiPAZ, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Molina-Ortiz
authors.forename: Ana
authors.initials: A
authors.lastname: Villarejo
authors.forename: Matthew
authors.initials: M
authors.lastname: MacPherson
authors.forename: Vanesa
authors.initials: V
authors.lastname: Santos
authors.forename: Amalia
authors.initials: A
authors.lastname: Montes
authors.forename: Serhiy
authors.initials: S
authors.lastname: Souchelnytskyi
authors.forename: Francisco
authors.initials: F
authors.lastname: Portillo
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D055550:Protein Stability; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D012694:Serine / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D012694:Serine