Sprouty1 is a broad mediator of cellular senescence.

Cellular Senescence Animals Mice Membrane Proteins / metabolism Humans Fibroblasts / metabolism Adaptor Proteins, Signal Transducing / metabolism Phosphoproteins / metabolism p38 Mitogen-Activated Protein Kinases / metabolism Intracellular Signaling Peptides and Proteins / metabolism MAP Kinase Signaling System Wound Healing

Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
26 Apr 2024
Historique:
received: 10 10 2023
accepted: 17 04 2024
revised: 12 04 2024
medline: 27 4 2024
pubmed: 27 4 2024
entrez: 26 4 2024
Statut: epublish

Résumé

Genes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains obscure. Here we show that Sprouty proteins are general mediators of cellular senescence. Induction of cellular senescence by several triggers in vitro correlates with upregulation of Sprouty protein levels. More importantly, overexpression of Sprouty genes is sufficient to cause premature cellular senescence, via a conserved N-terminal tyrosine (Tyrosine 53 of Sprouty1). Accordingly, fibroblasts from knockin animals lacking that tyrosine escape replicative senescence. In vivo, heterozygous knockin mice display delayed induction of cellular senescence during cutaneous wound healing and upon chemotherapy-induced cellular senescence. Unlike other functions of this family of genes, induction of cellular senescence appears to be independent of activation of the ERK1/2 pathway. Instead, we show that Sprouty proteins induce cellular senescence upstream of the p38 pathway in these in vitro and in vivo paradigms.

Identifiants

DOI: 10.1038/s41419-024-06689-4 PMID: 38670941
pubmed: 38670941
doi: 10.1038/s41419-024-06689-4
pii: 10.1038/s41419-024-06689-4
doi:

Substances chimiques

Membrane Proteins 0
Spry1 protein, mouse 0
Adaptor Proteins, Signal Transducing 0
Phosphoproteins 0
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24
Intracellular Signaling Peptides and Proteins 0
SPRY1 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

296

Subventions

Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : BFU2010-47175-P
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : BFU2017-83646-P
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2020-114947GB-I00

Informations de copyright

© 2024. The Author(s).

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Auteurs

Carlos Anerillas (C)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain. canerillas@cbm.csic.com.
Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD, USA. canerillas@cbm.csic.com.
Homeostasis de tejidos y órganos program, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC) - Universidad Autónoma de Madrid, Madrid, Spain. canerillas@cbm.csic.com.

Aida Perramon-Güell (A)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Gisela Altés (G)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Sara Cuesta (S)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.
Fundación de Investigación Biomédica de Cádiz, Hospital Universitario Puerta del Mar, Novena Planta, Investigación, Av Ana de Viya, 21, Cádiz, Spain.

Marta Vaquero (M)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.
Hospital Universitari Arnau de Vilanova, Rovira Roure, 80, Lleida, Spain.

Anna Olomí (A)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Ruth Rodríguez-Barrueco (R)

Laboratory of Precision Medicine, Oncobell Program. Bellvitge Biomedical Research Institute (IDIBELL), Gran via De l'Hospitalet, Barcelona, Spain.
ORCID: 0000-0003-4925-8865

David Llobet-Navàs (D)

Laboratory of Precision Medicine, Oncobell Program. Bellvitge Biomedical Research Institute (IDIBELL), Gran via De l'Hospitalet, Barcelona, Spain.
ORCID: 0000-0003-1443-7003

Joaquim Egea (J)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Xavi Dolcet (X)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Andrée Yeramian (A)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain.

Mario Encinas (M)

Developmental and Oncogenic Signaling Group, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Rovira Roure, 80, Lleida, Spain. mario.encinas@udl.cat.
ORCID: 0000-0003-3509-7431

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Eucaryotes › Animaux › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › Sprouty1 is a broad mediator of cellular senescence.
questionsmedicales.fr › Phénomènes biologiques › Régénération › Cicatrisation de plaie › Sprouty1 is a broad mediator of cellular senescence.