SOS GEFs in health and disease

SOS1 and SOS2 are the most universal and widely expressed family of guanine exchange factors (GEFs) capable or activating RAS or RAC1 proteins in metazoan cells. SOS proteins contain a sequence of modular domains that are responsible for different intramolecular and intermolecular interactions modul...

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Detalles Bibliográficos
Autores: Calvo Baltanás, Fernando, Zarich, N, Rojas-Cabaneros, JM, Santos, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/148084
Acceso en línea:https://hdl.handle.net/11441/148084
https://doi.org/10.1016/j.bbcan.2020.188445
Access Level:acceso abierto
Palabra clave:Cancer
RAS
RASGEF
Rasopathies
SOS1
SOS2
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repository_id_str
spelling SOS GEFs in health and diseaseCalvo Baltanás, FernandoZarich, NRojas-Cabaneros, JMSantos, ECancerRASRASGEFRasopathiesSOS1SOS2SOS1 and SOS2 are the most universal and widely expressed family of guanine exchange factors (GEFs) capable or activating RAS or RAC1 proteins in metazoan cells. SOS proteins contain a sequence of modular domains that are responsible for different intramolecular and intermolecular interactions modulating mechanisms of selfinhibition, allosteric activation and intracellular homeostasis. Despite their homology, analyses of SOS1/2-KO mice demonstrate functional prevalence of SOS1 over SOS2 in cellular processes including proliferation, migration, inflammation or maintenance of intracellular redox homeostasis, although some functional redundancy cannot be excluded, particularly at the organismal level. Specific SOS1 gain-of-function mutations have been identified in inherited RASopathies and various sporadic human cancers. SOS1 depletion reduces tumorigenesis mediated by RAS or RAC1 in mouse models and is associated with increased intracellular oxidative stress and mitochondrial dysfunction. Since WT RAS is essential for development of RAS-mutant tumors, the SOS GEFs may be considered as relevant biomarkers or therapy targets in RAS-dependent cancers. Inhibitors blocking SOS expression, intrinsic GEF activity, or productive SOS protein-protein interactions with cellular regulators and/or RAS/RAC targets have been recently developed and shown preclinical and clinical effectiveness blocking aberrant RAS signaling in RAS-driven and RTK-driven tumors.ElsevierFisiología Médica y BiofísicaAreces FoundationFEDER funds2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/148084https://doi.org/10.1016/j.bbcan.2020.188445reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1874 (2), 188445.CIVP19A5942https://www.sciencedirect.com/science/article/pii/S0304419X20301645?via%3Dihubinfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/1480842026-06-17T12:51:07Z
dc.title.none.fl_str_mv SOS GEFs in health and disease
title SOS GEFs in health and disease
spellingShingle SOS GEFs in health and disease
Calvo Baltanás, Fernando
Cancer
RAS
RASGEF
Rasopathies
SOS1
SOS2
title_short SOS GEFs in health and disease
title_full SOS GEFs in health and disease
title_fullStr SOS GEFs in health and disease
title_full_unstemmed SOS GEFs in health and disease
title_sort SOS GEFs in health and disease
dc.creator.none.fl_str_mv Calvo Baltanás, Fernando
Zarich, N
Rojas-Cabaneros, JM
Santos, E
author Calvo Baltanás, Fernando
author_facet Calvo Baltanás, Fernando
Zarich, N
Rojas-Cabaneros, JM
Santos, E
author_role author
author2 Zarich, N
Rojas-Cabaneros, JM
Santos, E
author2_role author
author
author
dc.contributor.none.fl_str_mv Fisiología Médica y Biofísica
Areces Foundation
FEDER funds
dc.subject.none.fl_str_mv Cancer
RAS
RASGEF
Rasopathies
SOS1
SOS2
topic Cancer
RAS
RASGEF
Rasopathies
SOS1
SOS2
description SOS1 and SOS2 are the most universal and widely expressed family of guanine exchange factors (GEFs) capable or activating RAS or RAC1 proteins in metazoan cells. SOS proteins contain a sequence of modular domains that are responsible for different intramolecular and intermolecular interactions modulating mechanisms of selfinhibition, allosteric activation and intracellular homeostasis. Despite their homology, analyses of SOS1/2-KO mice demonstrate functional prevalence of SOS1 over SOS2 in cellular processes including proliferation, migration, inflammation or maintenance of intracellular redox homeostasis, although some functional redundancy cannot be excluded, particularly at the organismal level. Specific SOS1 gain-of-function mutations have been identified in inherited RASopathies and various sporadic human cancers. SOS1 depletion reduces tumorigenesis mediated by RAS or RAC1 in mouse models and is associated with increased intracellular oxidative stress and mitochondrial dysfunction. Since WT RAS is essential for development of RAS-mutant tumors, the SOS GEFs may be considered as relevant biomarkers or therapy targets in RAS-dependent cancers. Inhibitors blocking SOS expression, intrinsic GEF activity, or productive SOS protein-protein interactions with cellular regulators and/or RAS/RAC targets have been recently developed and shown preclinical and clinical effectiveness blocking aberrant RAS signaling in RAS-driven and RTK-driven tumors.
publishDate 2020
dc.date.none.fl_str_mv 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/11441/148084
https://doi.org/10.1016/j.bbcan.2020.188445
url https://hdl.handle.net/11441/148084
https://doi.org/10.1016/j.bbcan.2020.188445
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1874 (2), 188445.
CIVP19A5942
https://www.sciencedirect.com/science/article/pii/S0304419X20301645?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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