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Sprouty1 is a broad mediator of cellular senescence.
- Source :
-
Cell death & disease [Cell Death Dis] 2024 Apr 26; Vol. 15 (4), pp. 296. Date of Electronic Publication: 2024 Apr 26. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Humans
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Signal Transducing genetics
Phosphoproteins metabolism
Phosphoproteins genetics
p38 Mitogen-Activated Protein Kinases metabolism
Intracellular Signaling Peptides and Proteins metabolism
Intracellular Signaling Peptides and Proteins genetics
MAP Kinase Signaling System
Wound Healing
Cellular Senescence
Membrane Proteins metabolism
Membrane Proteins genetics
Fibroblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 15
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 38670941
- Full Text :
- https://doi.org/10.1038/s41419-024-06689-4