A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX

The cellular response to p53 activation varies greatly in a stimulus‐ and cell type‐specific manner. Dissecting the molecular mechanisms defining these cell fate choices will assist the development of effective p53‐based cancer therapies and also illuminate fundamental processes by which gene networ...

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Detalles Bibliográficos
Autores: Henry, Ryan E, Andrysik, Zdenek, Paris, Ramiro, Galbraith, Matthew D., Espinosa, Joaquín M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/13372
Acceso en línea:http://hdl.handle.net/11336/13372
Access Level:acceso abierto
Palabra clave:Bax
Cell Fate Choice
Dr4
P53
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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network_acronym_str AR
network_name_str Argentina
repository_id_str
spelling A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAXHenry, Ryan EAndrysik, ZdenekParis, RamiroGalbraith, Matthew D.Espinosa, Joaquín M.BaxCell Fate ChoiceDr4P53https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The cellular response to p53 activation varies greatly in a stimulus‐ and cell type‐specific manner. Dissecting the molecular mechanisms defining these cell fate choices will assist the development of effective p53‐based cancer therapies and also illuminate fundamental processes by which gene networks control cellular behaviour. Using an experimental system wherein stimulus‐specific p53 responses are elicited by non‐genotoxic versus genotoxic agents, we discovered a novel mechanism that determines whether cells undergo proliferation arrest or cell death. Strikingly, we observe that key mediators of cell‐cycle arrest (p21, 14‐3‐3σ) and apoptosis (PUMA, BAX) are equally activated regardless of outcome. In fact, arresting cells display strong translocation of PUMA and BAX to the mitochondria, yet fail to release cytochrome C or activate caspases. Surprisingly, the key differential events in apoptotic cells are p53‐dependent activation of the DR4 death receptor pathway, caspase 8‐mediated cleavage of BID, and BID‐dependent activation of poised BAX at the mitochondria. These results reveal a previously unappreciated role for DR4 and the extrinsic apoptotic pathway in cell fate choice following p53 activation.Fil: Henry, Ryan E. State University Of Colorado-boulder; Estados UnidosFil: Andrysik, Zdenek. State University Of Colorado-boulder; Estados UnidosFil: Paris, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. State University Of Colorado-boulder; Estados UnidosFil: Galbraith, Matthew D.. State University Of Colorado-boulder; Estados UnidosFil: Espinosa, Joaquín M.. State University Of Colorado-boulder; Estados UnidosEmbo Press2012-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13372Henry, Ryan E; Andrysik, Zdenek; Paris, Ramiro; Galbraith, Matthew D.; Espinosa, Joaquín M.; A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX; Embo Press; Embo Journal; 31; 5; 3-2012; 1266-12780261-41891460-2075enginfo:eu-repo/semantics/altIdentifier/url/http://emboj.embopress.org/content/31/5/1266info:eu-repo/semantics/altIdentifier/doi/10.1038/emboj.2011.498info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:14:06Zoai:ri.conicet.gov.ar:11336/13372instacron: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:34982024-05-08 14:14:06.961CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
title A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
spellingShingle A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
Henry, Ryan E
Bax
Cell Fate Choice
Dr4
P53
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
title_full A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
title_fullStr A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
title_full_unstemmed A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
title_sort A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX
dc.creator.none.fl_str_mv Henry, Ryan E
Andrysik, Zdenek
Paris, Ramiro
Galbraith, Matthew D.
Espinosa, Joaquín M.
author Henry, Ryan E
author_facet Henry, Ryan E
Andrysik, Zdenek
Paris, Ramiro
Galbraith, Matthew D.
Espinosa, Joaquín M.
author_role author
author2 Andrysik, Zdenek
Paris, Ramiro
Galbraith, Matthew D.
Espinosa, Joaquín M.
author2_role author
author
author
author
dc.subject.none.fl_str_mv Bax
Cell Fate Choice
Dr4
P53
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic Bax
Cell Fate Choice
Dr4
P53
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description The cellular response to p53 activation varies greatly in a stimulus‐ and cell type‐specific manner. Dissecting the molecular mechanisms defining these cell fate choices will assist the development of effective p53‐based cancer therapies and also illuminate fundamental processes by which gene networks control cellular behaviour. Using an experimental system wherein stimulus‐specific p53 responses are elicited by non‐genotoxic versus genotoxic agents, we discovered a novel mechanism that determines whether cells undergo proliferation arrest or cell death. Strikingly, we observe that key mediators of cell‐cycle arrest (p21, 14‐3‐3σ) and apoptosis (PUMA, BAX) are equally activated regardless of outcome. In fact, arresting cells display strong translocation of PUMA and BAX to the mitochondria, yet fail to release cytochrome C or activate caspases. Surprisingly, the key differential events in apoptotic cells are p53‐dependent activation of the DR4 death receptor pathway, caspase 8‐mediated cleavage of BID, and BID‐dependent activation of poised BAX at the mitochondria. These results reveal a previously unappreciated role for DR4 and the extrinsic apoptotic pathway in cell fate choice following p53 activation.
publishDate 2012
dc.date.none.fl_str_mv 2012-03
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/11336/13372
Henry, Ryan E; Andrysik, Zdenek; Paris, Ramiro; Galbraith, Matthew D.; Espinosa, Joaquín M.; A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX; Embo Press; Embo Journal; 31; 5; 3-2012; 1266-1278
0261-4189
1460-2075
url http://hdl.handle.net/11336/13372
identifier_str_mv Henry, Ryan E; Andrysik, Zdenek; Paris, Ramiro; Galbraith, Matthew D.; Espinosa, Joaquín M.; A DR4:tBID axis drives the p53 apoptotic response by promoting oligomerization of poised BAX; Embo Press; Embo Journal; 31; 5; 3-2012; 1266-1278
0261-4189
1460-2075
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://emboj.embopress.org/content/31/5/1266
info:eu-repo/semantics/altIdentifier/doi/10.1038/emboj.2011.498
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Embo Press
publisher.none.fl_str_mv Embo Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
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score 15,812429

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