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Updated: Aug 1, 2025

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Casein kinase 1 gamma regulates oxidative stress response via interacting with the NADPH dual oxidase complex
Yiman Hu1, Zhaofa Xu1, Qian Pan1
1Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
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.
Insights
Casein kinase 1 gamma (CSNK-1) regulates oxidative stress and reactive oxygen species (ROS) levels in C. elegans. This finding reveals a conserved mechanism for maintaining ROS homeostasis.
Area of Science:
- Cellular Biology
- Genetics
- Biochemistry
Background:
- Oxidative stress is a critical biological process involving conserved regulatory mechanisms.
- Key regulators of oxidative stress response and reactive oxygen species (ROS) levels are not fully understood.
Purpose of the Study:
- To identify novel regulators of oxidative stress response and ROS homeostasis.
- To investigate the role of C. elegans casein kinase 1 gamma (CSNK-1) in oxidative stress.
Main Methods:
- Genetic nonallelic noncomplementation screens in C. elegans.
- Biochemical interaction assays.
- ROS level measurements in C. elegans and human cells.
- Nrf2 (SKN-1) interaction studies.
Main Results:
- CSNK-1 plays a novel role in regulating oxidative stress and ROS levels in C. elegans.
- CSNK-1 genetically interacts with NADPH dual oxidase genes (bli-3/tsp-15/doxa-1).
- Biochemical interactions were observed between CSNK-1 and DOXA-1, and their human orthologs.
- CSNK-1 is essential for normal ROS levels, and its human orthologs can modulate ROS.
- CSNK-1 interacts with Nrf2 (SKN-1) in oxidative stress response.
Conclusions:
- CSNK-1 (CSNK1G) represents a novel conserved regulator of ROS homeostasis.
- This discovery provides new insights into the fundamental mechanisms of oxidative stress response.
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