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Updated: May 24, 2026
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Multiple ShKT domain-containing MUL-1 proteins act as redox-responsive modulators of oxidative stress signaling in C.
Emilio Carranza-Garcia1, Abe Gayle Santos2, Kyoung-Hye Yoon3
1Center for Genomic Integrity, Institute for Basic Science, UNIST-gil 50, Ulsan 44919, Republic of Korea.
Abstract:
Organismal survival depends on coordinated responses to oxidative stress and DNA damage. Using Caenorhabditis elegans, we investigate mul-1, a robust transcriptional target of ionizing radiation and reactive oxygen species. Although annotated as a mucin, MUcin-Like 1 protein (MUL-1) is a small Stichodactyla helianthus K+ channel toxin (ShKT) domain-containing protein belonging to an invertebrate expanded family of cysteine-rich proteins. mul-1 is selectively induced by oxidative stress, including ionizing radiation, hydrogen peroxide, Pseudomonas aeruginosa infection, or loss of the peroxiredoxin PeRoxireDoXin-2 (PRDX-2), via the p38 Mitogen-Activated Protein Kinase-cAMP-dependent Transcription Factor (MAPK-ATF-7) pathway in intestinal cells. Loss of mul-1 and its paralogs increases reactive oxygen species accumulation, oxidative stress sensitivity, and C. Elegans P53-like protein (CEP-1)/p53-dependent germ cell apoptosis. Combined deletion of mul-1 paralogs causes constitutive apoptosis, reduced fecundity, and compensatory activation of abnormal DAuer Formation (DAF)-16/FoxO and SKiNhead-1 (SKN-1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) stress response pathways. Together with genetic analysis of SYstemic Stress signaling Mediator 1 (SYSM-1), these findings suggest MUL-1-like ShKT proteins buffer oxidative stress.
Insights
MUL-1 proteins, initially thought to be mucins, are key regulators of oxidative stress responses in C. elegans. These cysteine-rich proteins help prevent DNA damage and maintain organismal survival.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- Organismal survival relies on managing oxidative stress and DNA damage.
- MUL-1, a gene targeted by radiation and reactive oxygen species, was investigated in C. elegans.
- MUL-1 is a cysteine-rich protein with an ShKT domain, not a mucin.
Purpose of the Study:
- To investigate the function of the mul-1 gene and its protein product in response to oxidative stress.
- To elucidate the regulatory pathway involved in mul-1 induction.
- To understand the role of MUL-1-like proteins in cellular defense mechanisms.
Main Methods:
- Utilized Caenorhabditis elegans as a model organism.
- Studied gene expression changes in response to ionizing radiation (IR) and hydrogen peroxide (H2O2).
- Employed genetic analysis, including gene deletion and paralog analysis, and pathway analysis (p38 MAPK-ATF-7).
Main Results:
- mul-1 is selectively induced by oxidative stress via the p38 MAPK-ATF-7 pathway in intestinal cells.
- Loss of mul-1 and its paralogs leads to increased reactive oxygen species (ROS) accumulation and oxidative stress sensitivity.
- Deletion of mul-1 paralogs resulted in constitutive apoptosis, reduced fecundity, and activation of DAF-16/Foxo and SKN-1/Nrf2 pathways.
Conclusions:
- MUL-1-like ShKT proteins function as crucial buffers against oxidative stress.
- These proteins play a significant role in protecting cells from DNA damage and maintaining organismal health.
- The study reveals a novel role for ShKT domain proteins in stress response pathways.
