CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration

Autores
Abbas, Tarek; Mueller, Adam C.; Shibata, Etsuko; Keaton, Mignon; Rossi, Mario; Dutta, Anindya
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Cul4-Cdt2 (CRL4(Cdt2)) E3 ubiquitin ligase is a master regulator of cell-cycle progression and genome stability. Despite its central role in the degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8, little is known about the regulation of its activity. We report that Cdt2 is autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally polyubiquitylated and degraded by Cul1-FBXO11 (CRL1(FBXO11)). CRL1(FBXO11)-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is important during the response to TGF-β, with the Set8 induction being important for turning off the activation of Smad2. The migration of epithelial cells is also stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is an interesting example of cross-regulation between specific Cullin 4 and Cullin 1 E3 ubiquitin ligases and highlights the role of ubiquitylation in regulating cellular responses to TGF-β and the migration of epithelial cells.
Fil: Abbas, Tarek. University of Virginia; Estados Unidos
Fil: Mueller, Adam C.. University of Virginia; Estados Unidos
Fil: Shibata, Etsuko. University of Virginia; Estados Unidos
Fil: Keaton, Mignon. University of Virginia; Estados Unidos
Fil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Dutta, Anindya. University of Virginia; Estados Unidos
Materia
Histone Methyl transferase
Ubiquitin
Cellular invasion
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12300
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12300
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular MigrationAbbas, TarekMueller, Adam C.Shibata, EtsukoKeaton, MignonRossi, MarioDutta, AnindyaHistone Methyl transferaseUbiquitinCellular invasionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The Cul4-Cdt2 (CRL4(Cdt2)) E3 ubiquitin ligase is a master regulator of cell-cycle progression and genome stability. Despite its central role in the degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8, little is known about the regulation of its activity. We report that Cdt2 is autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally polyubiquitylated and degraded by Cul1-FBXO11 (CRL1(FBXO11)). CRL1(FBXO11)-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is important during the response to TGF-β, with the Set8 induction being important for turning off the activation of Smad2. The migration of epithelial cells is also stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is an interesting example of cross-regulation between specific Cullin 4 and Cullin 1 E3 ubiquitin ligases and highlights the role of ubiquitylation in regulating cellular responses to TGF-β and the migration of epithelial cells.Fil: Abbas, Tarek. University of Virginia; Estados UnidosFil: Mueller, Adam C.. University of Virginia; Estados UnidosFil: Shibata, Etsuko. University of Virginia; Estados UnidosFil: Keaton, Mignon. University of Virginia; Estados UnidosFil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Dutta, Anindya. University of Virginia; Estados UnidosCell Press2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12300Abbas, Tarek; Mueller, Adam C.; Shibata, Etsuko; Keaton, Mignon; Rossi, Mario; et al.; CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration; Cell Press; Molecular Cell; 49; 6; 3-2013; 1147-11581097-2765enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1097276513001305info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615078/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molcel.2013.02.003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:45:55Zoai:ri.conicet.gov.ar:11336/12300instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:45:55.608CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
title CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
spellingShingle CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
Abbas, Tarek
Histone Methyl transferase
Ubiquitin
Cellular invasion
title_short CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
title_full CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
title_fullStr CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
title_full_unstemmed CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
title_sort CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration
dc.creator.none.fl_str_mv Abbas, Tarek
Mueller, Adam C.
Shibata, Etsuko
Keaton, Mignon
Rossi, Mario
Dutta, Anindya
author Abbas, Tarek
author_facet Abbas, Tarek
Mueller, Adam C.
Shibata, Etsuko
Keaton, Mignon
Rossi, Mario
Dutta, Anindya
author_role author
author2 Mueller, Adam C.
Shibata, Etsuko
Keaton, Mignon
Rossi, Mario
Dutta, Anindya
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Histone Methyl transferase
Ubiquitin
Cellular invasion
topic Histone Methyl transferase
Ubiquitin
Cellular invasion
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The Cul4-Cdt2 (CRL4(Cdt2)) E3 ubiquitin ligase is a master regulator of cell-cycle progression and genome stability. Despite its central role in the degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8, little is known about the regulation of its activity. We report that Cdt2 is autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally polyubiquitylated and degraded by Cul1-FBXO11 (CRL1(FBXO11)). CRL1(FBXO11)-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is important during the response to TGF-β, with the Set8 induction being important for turning off the activation of Smad2. The migration of epithelial cells is also stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is an interesting example of cross-regulation between specific Cullin 4 and Cullin 1 E3 ubiquitin ligases and highlights the role of ubiquitylation in regulating cellular responses to TGF-β and the migration of epithelial cells.
Fil: Abbas, Tarek. University of Virginia; Estados Unidos
Fil: Mueller, Adam C.. University of Virginia; Estados Unidos
Fil: Shibata, Etsuko. University of Virginia; Estados Unidos
Fil: Keaton, Mignon. University of Virginia; Estados Unidos
Fil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Dutta, Anindya. University of Virginia; Estados Unidos
description The Cul4-Cdt2 (CRL4(Cdt2)) E3 ubiquitin ligase is a master regulator of cell-cycle progression and genome stability. Despite its central role in the degradation of many cell-cycle regulators, e.g., Cdt1, p21, and Pr-Set7/Set8, little is known about the regulation of its activity. We report that Cdt2 is autoubiquitylated by the CRL4A E3 ubiquitin ligase. Cdt2 is additionally polyubiquitylated and degraded by Cul1-FBXO11 (CRL1(FBXO11)). CRL1(FBXO11)-mediated degradation of Cdt2 stabilizes p21 and Set8, and this is important during the response to TGF-β, with the Set8 induction being important for turning off the activation of Smad2. The migration of epithelial cells is also stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. This is an interesting example of cross-regulation between specific Cullin 4 and Cullin 1 E3 ubiquitin ligases and highlights the role of ubiquitylation in regulating cellular responses to TGF-β and the migration of epithelial cells.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/12300
Abbas, Tarek; Mueller, Adam C.; Shibata, Etsuko; Keaton, Mignon; Rossi, Mario; et al.; CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration; Cell Press; Molecular Cell; 49; 6; 3-2013; 1147-1158
1097-2765
url http://hdl.handle.net/11336/12300
identifier_str_mv Abbas, Tarek; Mueller, Adam C.; Shibata, Etsuko; Keaton, Mignon; Rossi, Mario; et al.; CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration; Cell Press; Molecular Cell; 49; 6; 3-2013; 1147-1158
1097-2765
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1097276513001305
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615078/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molcel.2013.02.003
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782158148993024
score 12.982451

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