Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.

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 fun...

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Main Authors: Patricia Molina-Ortiz, Ana Villarejo, Matthew MacPherson, Vanesa Santos, Amalia Montes, Serhiy Souchelnytskyi, Francisco Portillo, Amparo Cano
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3342263?pdf=render
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author Patricia Molina-Ortiz
Ana Villarejo
Matthew MacPherson
Vanesa Santos
Amalia Montes
Serhiy Souchelnytskyi
Francisco Portillo
Amparo Cano
author_facet Patricia Molina-Ortiz
Ana Villarejo
Matthew MacPherson
Vanesa Santos
Amalia Montes
Serhiy Souchelnytskyi
Francisco Portillo
Amparo Cano
author_sort Patricia Molina-Ortiz
collection DOAJ
description 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.
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spelling doaj.art-ba67ed7f38d6452b84eef18b6a0b22262022-12-22T00:18:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3613210.1371/journal.pone.0036132Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.Patricia Molina-OrtizAna VillarejoMatthew MacPhersonVanesa SantosAmalia MontesSerhiy SouchelnytskyiFrancisco PortilloAmparo CanoSnail1 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.http://europepmc.org/articles/PMC3342263?pdf=render
spellingShingle Patricia Molina-Ortiz
Ana Villarejo
Matthew MacPherson
Vanesa Santos
Amalia Montes
Serhiy Souchelnytskyi
Francisco Portillo
Amparo Cano
Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
PLoS ONE
title Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
title_full Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
title_fullStr Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
title_full_unstemmed Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
title_short Characterization of the SNAG and SLUG domains of Snail2 in the repression of E-cadherin and EMT induction: modulation by serine 4 phosphorylation.
title_sort characterization of the snag and slug domains of snail2 in the repression of e cadherin and emt induction modulation by serine 4 phosphorylation
url http://europepmc.org/articles/PMC3342263?pdf=render
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