Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.

Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the acti...

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Detalles Bibliográficos
Autores: Burén, Stefan, Gomes, Ana L, Teijeiro, Ana, Fawal, Mohamad-Ali, Yilmaz, Mahmut, Tummala, Krishna S, Perez, Manuel, Rodriguez-Justo, Manuel, Campos Olivas, Ramon, Megias Vazquez, Diego, Djouder, Nabil
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17401
Acceso en línea:http://hdl.handle.net/20.500.12105/17401
Access Level:acceso abierto
Palabra clave:Animals
Glucose
Glucose Tolerance Test
HEK293 Cells
HeLa Cells
Humans
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spelling Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.Burén, StefanGomes, Ana LTeijeiro, AnaFawal, Mohamad-AliYilmaz, MahmutTummala, Krishna SPerez, ManuelRodriguez-Justo, ManuelCampos Olivas, RamonMegias Vazquez, DiegoDjouder, NabilAnimalsGlucoseGlucose Tolerance TestHEK293 CellsHeLa CellsHumansCancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations.Cell PressGobierno de EspañaWorldwide Cancer Research20242024-02-0120162016-08-0820162016-08-08journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/17401reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/174012026-06-12T12:43:37Z
dc.title.none.fl_str_mv Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
title Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
spellingShingle Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
Burén, Stefan
Animals
Glucose
Glucose Tolerance Test
HEK293 Cells
HeLa Cells
Humans
title_short Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
title_full Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
title_fullStr Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
title_full_unstemmed Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
title_sort Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms.
dc.creator.none.fl_str_mv Burén, Stefan
Gomes, Ana L
Teijeiro, Ana
Fawal, Mohamad-Ali
Yilmaz, Mahmut
Tummala, Krishna S
Perez, Manuel
Rodriguez-Justo, Manuel
Campos Olivas, Ramon
Megias Vazquez, Diego
Djouder, Nabil
author Burén, Stefan
author_facet Burén, Stefan
Gomes, Ana L
Teijeiro, Ana
Fawal, Mohamad-Ali
Yilmaz, Mahmut
Tummala, Krishna S
Perez, Manuel
Rodriguez-Justo, Manuel
Campos Olivas, Ramon
Megias Vazquez, Diego
Djouder, Nabil
author_role author
author2 Gomes, Ana L
Teijeiro, Ana
Fawal, Mohamad-Ali
Yilmaz, Mahmut
Tummala, Krishna S
Perez, Manuel
Rodriguez-Justo, Manuel
Campos Olivas, Ramon
Megias Vazquez, Diego
Djouder, Nabil
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Gobierno de España
Worldwide Cancer Research
dc.subject.none.fl_str_mv Animals
Glucose
Glucose Tolerance Test
HEK293 Cells
HeLa Cells
Humans
topic Animals
Glucose
Glucose Tolerance Test
HEK293 Cells
HeLa Cells
Humans
description Cancer cells can adapt and survive under low nutrient conditions, but underlying mechanisms remain poorly explored. We demonstrate here that glucose maintains a functional complex between the co-chaperone URI, PP1γ, and OGT, the enzyme catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA, which phosphorylates URI at Ser-371, resulting in PP1γ release and URI-mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c-MYC degradation to maintain cell survival. In the presence of glucose, PP1γ-bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non-phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-08-08
2016
2016-08-08
2024
2024-02-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17401
url http://hdl.handle.net/20.500.12105/17401
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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