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Stress sensitivity of a fission yeast strain lacking histidine kinases is rescued by the ectopic expression of Chk1 from Candida albicans
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
2017 (English)In: Current Genetics, ISSN 0172-8083, E-ISSN 1432-0983, Vol. 63, no 2, 343-357 p.Article in journal (Refereed) Published
Abstract [en]

The development of new drugs against the pathogenic yeast Candida albicans is compelling and the evolution of relevant bioassays is important to achieve this goal. Promising drug targets are proteins that lack human counterparts which are true for the His-to-Asp phosphorelay signal transduction systems, important for stress sensing in bacteria, fungi, and plants. In the pathogenic yeast, Candida albicans, the CaChk1 histidine kinase is a trigger of the pathway that leads to a switch from yeast to hyphal growth necessary for invasion. Intriguingly, the model yeast Schizosaccharomyces pombe has a similar phosphorelay system, with three histidine kinases named Mak1, Mak2, and Mak3, which are important for the prevention of aberrant mating and sporulation on rich media. This study uncovered distinct functions for the three histidine kinases; Mak1 alone or Mak2 and Mak3 together were sufficient for the repression of the meiotic cycle when nutrients were available. Moreover, strains lacking histidine kinase genes were sensitive to various types of stress conditions in an auxotrophic strain background, while the stress sensitivity was lost in prototrophic strains. Finally, the stress sensitivity of a S. pombe strain that lacks endogenous histidine kinases could be complemented by the ectopic expression of the CaChk1 histidine kinase from C. albicans. This finding opens up for the possibility to perform a drug screen with a biological read-out in S. pombe to find inhibitors of CaChk1.

Place, publisher, year, edition, pages
SPRINGER , 2017. Vol. 63, no 2, 343-357 p.
Keyword [en]
Histidine kinase, Candida albicans, Fission yeast, Schizosaccharomyces pombe, His-to-Asp phosphorelay, Stress response
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-321786DOI: 10.1007/s00294-016-0644-9ISI: 000399176400018PubMedID: 27613427OAI: oai:DiVA.org:uu-321786DiVA: diva2:1094795
Funder
Swedish Research Council, 621-2011-4688
Note

V. Maksimov and M. Wäneskog contributed equally.

Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2017-05-11Bibliographically approved

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Maksimov, VladimirWäneskog, MarcusRodriguez, AlejandroBjerling, Pernilla
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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLabDepartment of Cell and Molecular Biology
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