Large-scale genetic screens identify BET-1 as a cytoskeleton regulator promoting actin function and life span.
CRISPR
actin
aging
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
17
10
2022
received:
09
08
2022
accepted:
01
11
2022
pubmed:
21
11
2022
medline:
17
1
2023
entrez:
20
11
2022
Statut:
ppublish
Résumé
The actin cytoskeleton is a three-dimensional scaffold of proteins that is a regulatory, energyconsuming network with dynamic properties to shape the structure and function of the cell. Proper actin function is required for many cellular pathways, including cell division, autophagy, chaperone function, endocytosis, and exocytosis. Deterioration of these processes manifests during aging and exposure to stress, which is in part due to the breakdown of the actin cytoskeleton. However, the regulatory mechanisms involved in preservation of cytoskeletal form and function are not well-understood. Here, we performed a multipronged, cross-organismal screen combining a whole-genome CRISPR-Cas9 screen in human fibroblasts with in vivo Caenorhabditis elegans synthetic lethality screening. We identified the bromodomain protein, BET-1, as a key regulator of actin function and longevity. Overexpression of bet-1 preserves actin function at late age and promotes life span and healthspan in C. elegans. These beneficial effects are mediated through actin preservation by the transcriptional regulator function of BET-1. Together, our discovery assigns a key role for BET-1 in cytoskeletal health, highlighting regulatory cellular networks promoting cytoskeletal homeostasis.
Identifiants
pubmed: 36404134
doi: 10.1111/acel.13742
pmc: PMC9835578
doi:
Substances chimiques
Actins
0
Caenorhabditis elegans Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13742Subventions
Organisme : NIA NIH HHS
ID : T32 AG052374
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG065200
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG071861
Pays : United States
Informations de copyright
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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