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Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A

Snail1 is a major factor for epithelial-mesenchymal transition (EMT), an important event in tumor metastasis and in other pathologies. Snail1 is tightly regulated at transcriptional and posttranscriptional levels. Control of Snail1 protein stability and nuclear export by GSK3β phosphorylation is imp...

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Autores principales: MacPherson, Matthew Reid, Molina, Patricia, Souchelnytskyi, Serhiy, Wernstedt, Christer, Martin-Pérez, Jorge, Portillo, Francisco, Cano, Amparo
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808231/
https://www.ncbi.nlm.nih.gov/pubmed/19923321
http://dx.doi.org/10.1091/mbc.E09-06-0504
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author MacPherson, Matthew Reid
Molina, Patricia
Souchelnytskyi, Serhiy
Wernstedt, Christer
Martin-Pérez, Jorge
Portillo, Francisco
Cano, Amparo
author_facet MacPherson, Matthew Reid
Molina, Patricia
Souchelnytskyi, Serhiy
Wernstedt, Christer
Martin-Pérez, Jorge
Portillo, Francisco
Cano, Amparo
author_sort MacPherson, Matthew Reid
collection PubMed
description Snail1 is a major factor for epithelial-mesenchymal transition (EMT), an important event in tumor metastasis and in other pathologies. Snail1 is tightly regulated at transcriptional and posttranscriptional levels. Control of Snail1 protein stability and nuclear export by GSK3β phosphorylation is important for Snail1 functionality. Stabilization mechanisms independent of GSK3β have also been reported, including interaction with LOXL2 or regulation of the COP9 signalosome by inflammatory signals. To get further insights into the role of Snail1 phosphorylation, we have performed an in-depth analysis of in vivo human Snail1 phosphorylation combined with mutational studies. We identify new phosphorylation sites at serines 11, 82, and 92 and confirmed previously suggested phosphorylations at serine 104 and 107. Serines 11 and 92 participate in the control of Snail1 stability and positively regulate Snail1 repressive function and its interaction with mSin3A corepressor. Furthermore, serines 11 and 92 are required for Snail1-mediated EMT and cell viability, respectively. PKA and CK2 have been characterized as the main kinases responsible for in vitro Snail1 phosphorylation at serine 11 and 92, respectively. These results highlight serines 11 and 92 as new players in Snail1 regulation and suggest the participation of CK2 and PKA in the modulation of Snail1 functionality.
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spelling pubmed-28082312010-03-30 Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A MacPherson, Matthew Reid Molina, Patricia Souchelnytskyi, Serhiy Wernstedt, Christer Martin-Pérez, Jorge Portillo, Francisco Cano, Amparo Mol Biol Cell Articles Snail1 is a major factor for epithelial-mesenchymal transition (EMT), an important event in tumor metastasis and in other pathologies. Snail1 is tightly regulated at transcriptional and posttranscriptional levels. Control of Snail1 protein stability and nuclear export by GSK3β phosphorylation is important for Snail1 functionality. Stabilization mechanisms independent of GSK3β have also been reported, including interaction with LOXL2 or regulation of the COP9 signalosome by inflammatory signals. To get further insights into the role of Snail1 phosphorylation, we have performed an in-depth analysis of in vivo human Snail1 phosphorylation combined with mutational studies. We identify new phosphorylation sites at serines 11, 82, and 92 and confirmed previously suggested phosphorylations at serine 104 and 107. Serines 11 and 92 participate in the control of Snail1 stability and positively regulate Snail1 repressive function and its interaction with mSin3A corepressor. Furthermore, serines 11 and 92 are required for Snail1-mediated EMT and cell viability, respectively. PKA and CK2 have been characterized as the main kinases responsible for in vitro Snail1 phosphorylation at serine 11 and 92, respectively. These results highlight serines 11 and 92 as new players in Snail1 regulation and suggest the participation of CK2 and PKA in the modulation of Snail1 functionality. The American Society for Cell Biology 2010-01-15 /pmc/articles/PMC2808231/ /pubmed/19923321 http://dx.doi.org/10.1091/mbc.E09-06-0504 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
MacPherson, Matthew Reid
Molina, Patricia
Souchelnytskyi, Serhiy
Wernstedt, Christer
Martin-Pérez, Jorge
Portillo, Francisco
Cano, Amparo
Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title_full Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title_fullStr Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title_full_unstemmed Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title_short Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A
title_sort phosphorylation of serine 11 and serine 92 as new positive regulators of human snail1 function: potential involvement of casein kinase-2 and the camp-activated kinase protein kinase a
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808231/
https://www.ncbi.nlm.nih.gov/pubmed/19923321
http://dx.doi.org/10.1091/mbc.E09-06-0504
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