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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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Autores principales: Molina-Ortiz, Patricia, Villarejo, Ana, MacPherson, Matthew, Santos, Vanesa, Montes, Amalia, Souchelnytskyi, Serhiy, Portillo, Francisco, Cano, Amparo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342263/
https://www.ncbi.nlm.nih.gov/pubmed/22567133
http://dx.doi.org/10.1371/journal.pone.0036132
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author Molina-Ortiz, Patricia
Villarejo, Ana
MacPherson, Matthew
Santos, Vanesa
Montes, Amalia
Souchelnytskyi, Serhiy
Portillo, Francisco
Cano, Amparo
author_facet Molina-Ortiz, Patricia
Villarejo, Ana
MacPherson, Matthew
Santos, Vanesa
Montes, Amalia
Souchelnytskyi, Serhiy
Portillo, Francisco
Cano, Amparo
author_sort Molina-Ortiz, Patricia
collection PubMed
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 pubmed-33422632012-05-07 Characterization of the SNAG and SLUG Domains of Snail2 in the Repression of E-Cadherin and EMT Induction: Modulation by Serine 4 Phosphorylation Molina-Ortiz, Patricia Villarejo, Ana MacPherson, Matthew Santos, Vanesa Montes, Amalia Souchelnytskyi, Serhiy Portillo, Francisco Cano, Amparo PLoS One Research Article 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. Public Library of Science 2012-05-02 /pmc/articles/PMC3342263/ /pubmed/22567133 http://dx.doi.org/10.1371/journal.pone.0036132 Text en Molina-Ortiz et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Molina-Ortiz, Patricia
Villarejo, Ana
MacPherson, Matthew
Santos, Vanesa
Montes, Amalia
Souchelnytskyi, Serhiy
Portillo, Francisco
Cano, Amparo
Characterization of the SNAG and SLUG Domains of Snail2 in the Repression of E-Cadherin and EMT Induction: Modulation by Serine 4 Phosphorylation
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342263/
https://www.ncbi.nlm.nih.gov/pubmed/22567133
http://dx.doi.org/10.1371/journal.pone.0036132
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