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Updated: Feb 5, 2026

Genetic Screen for Identification of Multicopy Suppressors in Schizosaccharomyces pombe
Published on: September 13, 2022
Cmk2 kinase is essential for survival in arsenite by modulating translation together with RACK1 orthologue Cpc2 in
Marta Sanchez-Marinas1, David Gimenez-Zaragoza1, Edgar Martin-Ramos1
1Department of Biomedical Sciences, Facultat de Medicina, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), CIBERONC, Barcelona 08036, Catalunya, Spain.
Abstract:
Different studies have demonstrated multiple effects of arsenite on human physiology. However, there are many open questions concerning the mechanism of response to arsenite. Schizosaccharomyces pombe activates the Sty1 MAPK pathway as a common response to several stress conditions. The specificity of the response is due to the activation of different transcription factors and specific targets such the Cmk2 MAPKAP kinase. We have previously shown that Cmk2 is phosphorylated and activated by the MAPK Sty1 in response to oxidative stress. Here, we report that Cmk2 kinase is specifically necessary to overcome the stress caused by metalloid agents, in particular arsenite. Deletion of cmk2 increases the protein level of various components of the MAPK pathway. Moreover, Cmk2 negatively regulates translation through the Cpc2 kinase: the RACK1 orthologue in fission yeast. RACK1 is a receptor for activated C-kinase. Interestingly, RACK1 is a constituent of the eukaryotic ribosome specifically localized in the head region of the 40 S subunit. Cmk2 controls arsenite response through Cpc2 and it does so through Cpc2 ribosomal function, as observed in genetic analysis using a Cpc2 mutant unable to bind to ribosome. These findings suggest a role for Cmk2 in regulating translation and facilitating adaptation to arsenite stress in the ribosome.
Insights
The Cmk2 kinase is crucial for fission yeast to survive arsenite stress by regulating translation. It controls the Cpc2 kinase, which functions on ribosomes to aid adaptation to metalloid agents.
Area of Science:
- Cellular stress response
- Molecular biology
- Yeast genetics
Background:
- Arsenite exposure causes physiological effects, but response mechanisms remain unclear.
- The Sty1 MAPK pathway in Schizosaccharomyces pombe mediates stress responses.
- Cmk2 kinase, activated by Sty1, is a target in stress signaling.
Purpose of the Study:
- Investigate the specific role of Cmk2 kinase in arsenite stress response.
- Elucidate the mechanism by which Cmk2 facilitates adaptation to metalloid agents.
- Determine the involvement of Cpc2 kinase and ribosomal function in Cmk2-mediated stress response.
Main Methods:
- Genetic analysis of Schizosaccharomyces pombe strains, including deletion mutants.
- Western blotting to assess protein levels within the MAPK pathway.
- Functional analysis of a Cpc2 mutant with impaired ribosome binding.
Main Results:
- Cmk2 kinase is essential for overcoming arsenite-induced stress in fission yeast.
- Deletion of cmk2 leads to increased levels of MAPK pathway components.
- Cmk2 regulates translation via Cpc2 kinase, which is functionally linked to ribosome activity.
Conclusions:
- Cmk2 plays a specific role in adapting to arsenite stress, distinct from general oxidative stress response.
- Cmk2 controls arsenite tolerance through Cpc2's function on the ribosome.
- These findings highlight a novel mechanism involving ribosomal regulation for adaptation to metalloid stress.
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