Casein kinase 1 gamma regulates oxidative stress response via interacting with the NADPH dual oxidase complex.
PLoS Genet
; 19(4): e1010740, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-37099597
ABSTRACT
Oxidative stress response is a fundamental biological process mediated by conserved mechanisms. The identities and functions of some key regulators remain unknown. Here, we report a novel role of C. elegans casein kinase 1 gamma CSNK-1 (also known as CK1γ or CSNK1G) in regulating oxidative stress response and ROS levels. csnk-1 interacted with the bli-3/tsp-15/doxa-1 NADPH dual oxidase genes via genetic nonallelic noncomplementation to affect C. elegans survival in oxidative stress. The genetic interaction was supported by specific biochemical interactions between DOXA-1 and CSNK-1 and potentially between their human orthologs DUOXA2 and CSNK1G2. Consistently, CSNK-1 was required for normal ROS levels in C. elegans. CSNK1G2 and DUOXA2 each can promote ROS levels in human cells, effects that were suppressed by a small molecule casein kinase 1 inhibitor. We also detected genetic interactions between csnk-1 and skn-1 Nrf2 in oxidative stress response. Together, we propose that CSNK-1 CSNK1G defines a novel conserved regulatory mechanism for ROS homeostasis.
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Base de dados:
MEDLINE
Assunto principal:
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article