The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling

Protein modifications by phosphorylation or ubiquitylation have been selected throughout evolution as efficient regulatory mechanisms of cellular processes. Cell migration is a complex, highly coordinated process where these mechanisms must participate in an integrated manner to transmit signaling d...

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Detalhes bibliográficos
Autores: Pedrazza, Leonardo, Schneider, Taiane, Bartrons Bach, Ramon, Ventura Pujol, Francesc
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/169988
Acesso em linha:https://hdl.handle.net/2445/169988
Access Level:acceso abierto
Palavra-chave:Ubiqüitina
Migració cel·lular
Ubiquitin
Cell migration
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spelling The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signalingPedrazza, LeonardoSchneider, TaianeBartrons Bach, RamonVentura Pujol, FrancescUbiqüitinaMigració cel·lularUbiquitinCell migrationProtein modifications by phosphorylation or ubiquitylation have been selected throughout evolution as efficient regulatory mechanisms of cellular processes. Cell migration is a complex, highly coordinated process where these mechanisms must participate in an integrated manner to transmit signaling during migration. In this study, we show that the ubiquitin ligase HERC1 regulates the p38 signaling pathway, and that this regulation is mediated by the MAPK kinase MKK3. Moreover, we demonstrate a crosstalk between RAF and MKK3/p38 pathways where RAF acts upstream of MKK3. Mechanistically, HERC1 regulates the protein levels of C-RAF and MKK3. Thus, HERC1 ubiquitylates C-RAF, targeting it for proteasomal degradation, and RAF proteins regulate MKK3 mRNA levels. Accordingly, HERC1 knockdown induces C-RAF stabilization and activation of RAF proteins; in turn, this activation increases MKK3, which phosphorylates and activates p38. The importance of these observations is demonstrated by HERC1 regulation of cell migration through regulation of p38 signaling via a RAF-dependent mechanism. Thus, HERC1 plays an essential role as a regulator of crosstalk between RAF/MKK3/p38 signaling pathways during cell migration.Nature Publishing Group2020202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/169988Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41598-020-57756-7Scientific Reports, 2020, vol. 10, p. 824https://doi.org/10.1038/s41598-020-57756-7cc-by (c) Pedrazza, Leonardo et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1699882026-05-29T05:05:01Z
dc.title.none.fl_str_mv The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
title The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
spellingShingle The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
Pedrazza, Leonardo
Ubiqüitina
Migració cel·lular
Ubiquitin
Cell migration
title_short The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
title_full The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
title_fullStr The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
title_full_unstemmed The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
title_sort The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling
dc.creator.none.fl_str_mv Pedrazza, Leonardo
Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
author Pedrazza, Leonardo
author_facet Pedrazza, Leonardo
Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
author_role author
author2 Schneider, Taiane
Bartrons Bach, Ramon
Ventura Pujol, Francesc
author2_role author
author
author
dc.subject.none.fl_str_mv Ubiqüitina
Migració cel·lular
Ubiquitin
Cell migration
topic Ubiqüitina
Migració cel·lular
Ubiquitin
Cell migration
description Protein modifications by phosphorylation or ubiquitylation have been selected throughout evolution as efficient regulatory mechanisms of cellular processes. Cell migration is a complex, highly coordinated process where these mechanisms must participate in an integrated manner to transmit signaling during migration. In this study, we show that the ubiquitin ligase HERC1 regulates the p38 signaling pathway, and that this regulation is mediated by the MAPK kinase MKK3. Moreover, we demonstrate a crosstalk between RAF and MKK3/p38 pathways where RAF acts upstream of MKK3. Mechanistically, HERC1 regulates the protein levels of C-RAF and MKK3. Thus, HERC1 ubiquitylates C-RAF, targeting it for proteasomal degradation, and RAF proteins regulate MKK3 mRNA levels. Accordingly, HERC1 knockdown induces C-RAF stabilization and activation of RAF proteins; in turn, this activation increases MKK3, which phosphorylates and activates p38. The importance of these observations is demonstrated by HERC1 regulation of cell migration through regulation of p38 signaling via a RAF-dependent mechanism. Thus, HERC1 plays an essential role as a regulator of crosstalk between RAF/MKK3/p38 signaling pathways during cell migration.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/169988
url https://hdl.handle.net/2445/169988
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-020-57756-7
Scientific Reports, 2020, vol. 10, p. 824
https://doi.org/10.1038/s41598-020-57756-7
dc.rights.none.fl_str_mv cc-by (c) Pedrazza, Leonardo et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Pedrazza, Leonardo et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,223283

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