CD95/Fas stoichiometry in future precision medicine

Autores
Sica, Mauricio Pablo; Roussel, Murielle; Legembre, Patrick
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CD95, also known as Fas, belongs to the tumor necrosis factor (TNF) receptor superfamily. The main biological function of this receptor is to orchestrate and control the immune response since mutations in CD95 or deregulation of its downstream signaling pathways lead to auto-immunity and inflammation. Interestingly, more than twenty years ago, pioneer studies highlighted that like TNFR1, TRAILR1 or CD40, CD95 pre-associates at the plasma membrane in a ligand-independent fashion. This self-association occurs through a domain designated pre-ligand assembly domain or PLAD. Although the disruption of this pre-association prevents CD95 signaling, no drugs targeting this region have been generated because many questions remain on the stoichiometry and conformation of this receptor. Despite more than 40.000 publications, no crystal structure of CD95 alone or in combination with its ligand, CD95L, exists. Based on other TNFR members, we herein discuss the predicted conformation of CD95 at the plasma membrane and how these putative structures might account for the induction of the cell signaling pathways.
Fil: Sica, Mauricio Pablo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina
Fil: Roussel, Murielle. Centre National de la Recherche Scientifique; Francia
Fil: Legembre, Patrick. Centre National de la Recherche Scientifique; Francia
Materia
CD95
CANCER
ARTIFICIAL INTELIGENCE
PROTEIN INTERACTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/272885
Acceder
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spelling CD95/Fas stoichiometry in future precision medicineSica, Mauricio PabloRoussel, MurielleLegembre, PatrickCD95CANCERARTIFICIAL INTELIGENCEPROTEIN INTERACTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1CD95, also known as Fas, belongs to the tumor necrosis factor (TNF) receptor superfamily. The main biological function of this receptor is to orchestrate and control the immune response since mutations in CD95 or deregulation of its downstream signaling pathways lead to auto-immunity and inflammation. Interestingly, more than twenty years ago, pioneer studies highlighted that like TNFR1, TRAILR1 or CD40, CD95 pre-associates at the plasma membrane in a ligand-independent fashion. This self-association occurs through a domain designated pre-ligand assembly domain or PLAD. Although the disruption of this pre-association prevents CD95 signaling, no drugs targeting this region have been generated because many questions remain on the stoichiometry and conformation of this receptor. Despite more than 40.000 publications, no crystal structure of CD95 alone or in combination with its ligand, CD95L, exists. Based on other TNFR members, we herein discuss the predicted conformation of CD95 at the plasma membrane and how these putative structures might account for the induction of the cell signaling pathways.Fil: Sica, Mauricio Pablo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Roussel, Murielle. Centre National de la Recherche Scientifique; FranciaFil: Legembre, Patrick. Centre National de la Recherche Scientifique; FranciaNature Publishing Group2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/272885Sica, Mauricio Pablo; Roussel, Murielle; Legembre, Patrick; CD95/Fas stoichiometry in future precision medicine; Nature Publishing Group; Cell Death and Differentiation; 32; 9; 4-2025; 1570-15771350-9047CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41418-025-01493-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41418-025-01493-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:14:49Zoai:ri.conicet.gov.ar:11336/272885instacron: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:34982025-10-15 15:14:49.889CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD95/Fas stoichiometry in future precision medicine
title CD95/Fas stoichiometry in future precision medicine
spellingShingle CD95/Fas stoichiometry in future precision medicine
Sica, Mauricio Pablo
CD95
CANCER
ARTIFICIAL INTELIGENCE
PROTEIN INTERACTION
title_short CD95/Fas stoichiometry in future precision medicine
title_full CD95/Fas stoichiometry in future precision medicine
title_fullStr CD95/Fas stoichiometry in future precision medicine
title_full_unstemmed CD95/Fas stoichiometry in future precision medicine
title_sort CD95/Fas stoichiometry in future precision medicine
dc.creator.none.fl_str_mv Sica, Mauricio Pablo
Roussel, Murielle
Legembre, Patrick
author Sica, Mauricio Pablo
author_facet Sica, Mauricio Pablo
Roussel, Murielle
Legembre, Patrick
author_role author
author2 Roussel, Murielle
Legembre, Patrick
author2_role author
author
dc.subject.none.fl_str_mv CD95
CANCER
ARTIFICIAL INTELIGENCE
PROTEIN INTERACTION
topic CD95
CANCER
ARTIFICIAL INTELIGENCE
PROTEIN INTERACTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv CD95, also known as Fas, belongs to the tumor necrosis factor (TNF) receptor superfamily. The main biological function of this receptor is to orchestrate and control the immune response since mutations in CD95 or deregulation of its downstream signaling pathways lead to auto-immunity and inflammation. Interestingly, more than twenty years ago, pioneer studies highlighted that like TNFR1, TRAILR1 or CD40, CD95 pre-associates at the plasma membrane in a ligand-independent fashion. This self-association occurs through a domain designated pre-ligand assembly domain or PLAD. Although the disruption of this pre-association prevents CD95 signaling, no drugs targeting this region have been generated because many questions remain on the stoichiometry and conformation of this receptor. Despite more than 40.000 publications, no crystal structure of CD95 alone or in combination with its ligand, CD95L, exists. Based on other TNFR members, we herein discuss the predicted conformation of CD95 at the plasma membrane and how these putative structures might account for the induction of the cell signaling pathways.
Fil: Sica, Mauricio Pablo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina
Fil: Roussel, Murielle. Centre National de la Recherche Scientifique; Francia
Fil: Legembre, Patrick. Centre National de la Recherche Scientifique; Francia
description CD95, also known as Fas, belongs to the tumor necrosis factor (TNF) receptor superfamily. The main biological function of this receptor is to orchestrate and control the immune response since mutations in CD95 or deregulation of its downstream signaling pathways lead to auto-immunity and inflammation. Interestingly, more than twenty years ago, pioneer studies highlighted that like TNFR1, TRAILR1 or CD40, CD95 pre-associates at the plasma membrane in a ligand-independent fashion. This self-association occurs through a domain designated pre-ligand assembly domain or PLAD. Although the disruption of this pre-association prevents CD95 signaling, no drugs targeting this region have been generated because many questions remain on the stoichiometry and conformation of this receptor. Despite more than 40.000 publications, no crystal structure of CD95 alone or in combination with its ligand, CD95L, exists. Based on other TNFR members, we herein discuss the predicted conformation of CD95 at the plasma membrane and how these putative structures might account for the induction of the cell signaling pathways.
publishDate 2025
dc.date.none.fl_str_mv 2025-04
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/11336/272885
Sica, Mauricio Pablo; Roussel, Murielle; Legembre, Patrick; CD95/Fas stoichiometry in future precision medicine; Nature Publishing Group; Cell Death and Differentiation; 32; 9; 4-2025; 1570-1577
1350-9047
CONICET Digital
CONICET
url http://hdl.handle.net/11336/272885
identifier_str_mv Sica, Mauricio Pablo; Roussel, Murielle; Legembre, Patrick; CD95/Fas stoichiometry in future precision medicine; Nature Publishing Group; Cell Death and Differentiation; 32; 9; 4-2025; 1570-1577
1350-9047
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41418-025-01493-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41418-025-01493-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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 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
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score 13.22299

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