Large‐scale genetic screens identify BET ‐1 as a cytoskeleton regulator promoting actin function and life span

Autor: Gilberto Garcia, Raz Bar‐Ziv, Maxim Averbukh, Nirmalya Dasgupta, Naibedya Dutta, Hanlin Zhang, Wudi Fan, Darius Moaddeli, C. Kimberly Tsui, Toni Castro Torres, Athena Alcala, Erica A. Moehle, Sally Hoang, Ophir Shalem, Peter D. Adams, Max A. Thorwald, Ryo Higuchi‐Sanabria
Rok vydání: 2022
Předmět:
Zdroj: Aging Cell. 22
ISSN: 1474-9726
1474-9718
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: