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Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast
1Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
In fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase, which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25 tyrosine phosphatase. This control network integrates many signals, including those that monitor DNA replication, DNA damage and cell size. We report here that a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes in the extracellular environment that affect cell physiology. Fission yeast spc1- mutants have a G2 delay that is greatly exacerbated by growth in high osmolarity media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis. Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation. Spc1 is inactivated by Pyp1, a phosphatase previously identified as a mitotic inhibitor. Pyp1 dephosphorylates only tyrosine-173 of Spc1, unlike the dual-specificity phosphatases that have been shown to regulate other MAP kinases.
Insights
Fission yeast Spc1 (MAP kinase pathway) links cell cycle control to environmental changes. Spc1 promotes mitosis, responding to osmotic stress and nutrient limitation.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- The cell cycle, particularly the G2/M transition, is tightly regulated by kinases and phosphatases.
- Environmental factors like osmolarity and nutrient availability can influence cell cycle progression.
- The fission yeast Cdc2/Cdc13 kinase complex controls mitotic entry, with regulation by Wee1/Mik1 and Cdc25.
Purpose of the Study:
- To investigate the role of the Spc1 MAP kinase pathway in integrating cell cycle control with environmental signals.
- To determine how Spc1 influences the G2/M transition in fission yeast.
- To elucidate the regulatory mechanisms of Spc1 activation and inactivation.
Main Methods:
- Analysis of spc1 mutants under various growth conditions (high osmolarity, nutrient limitation).
- Genetic interaction studies between spc1 and cdc25 mutations.
- Identification of kinases (Wis1) and phosphatases (Pyp1) involved in Spc1 regulation.
Main Results:
- spc1 mutants exhibit a G2 delay, exacerbated by high osmolarity and nutrient limitation.
- A lethal interaction between spc1 and cdc25 mutations indicates Spc1 promotes mitosis.
- Spc1 is activated by Wis1 kinase under stress conditions and inactivated by Pyp1 phosphatase.
- Pyp1 specifically dephosphorylates tyrosine-173 of Spc1.
Conclusions:
- The fission yeast MAP kinase pathway (Spc1) serves as a crucial link between environmental sensing and cell cycle progression.
- Spc1 plays a positive role in promoting the onset of mitosis.
- Spc1 regulation involves specific activation by Wis1 and inactivation by Pyp1, targeting a key regulatory residue.