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Cell Cycle Regulation and Hypoxic Adaptation in the Pathogenic Yeast Cryptococcus neoformans
Author(s) -
Kawamoto Susumu,
Moranova Zuzana,
Virtudazo Eric,
Ohusu Misako,
Raclavsky Vladislav
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.533.30
Subject(s) - cryptococcus neoformans , biology , cyclin dependent kinase 1 , cdc25 , saccharomyces cerevisiae , cell cycle , wee1 , transcription factor , microbiology and biotechnology , cell cycle checkpoint , yeast , gene , genetics
We have reported that the cell cycle behavior of the pathogenic yeast Cryptococcus neoformans ( C. neoformans) is different from the cell cycle control exhibited by the model yeast Saccharomyces cerevisiae, and also have reported the molecular characterization and physiological roles of the two main eukaryotic cell cycle genes, C. neoformans cyclin dependent kinase 1 (CnCdk1) and cyclin homologues. We also identified components of the G2‐M control machinery, Wee1 kinase and Cdc25 phosphatase homologues, in C. neoformans . Wee1 and Cdc25 are involved in the inhibition and activation, respectively, of the Cdk1‐cyclin complex at the mitotic entry checkpoint in eukaryotes. On the other hand, in the obligate aerobic pathogenic yeast C. neoformans , limited aeration has been demonstrated to cause slowdown in proliferation and delayed budding, resulting eventually in a unique unbudded G2‐arrest. The ability to adapt to decreased oxygen levels during pathogenesis has been identified as a virulence factor in C. neoformans . We have identified and characterized the gene that is necessary for the proliferation slowdown and G2‐arrest caused by limited aeration. Random mutants were prepared and screened for lack of typical slowdown of proliferation under limited aeration. The gene coding for a zinc‐finger transcription factor was identified in mutants showing most distinctive phenotype. Targeted deletion strain and reconstituted strain were prepared to characterize and confirm the gene functions. This gene was also identified in a parallel studies as homologous both to calcineurin responsive (Crz1) and PKC1‐dependent (SP1‐like) transcription factors. We have confirmed the role of the cryptococcal homologue of CRZ1/SP1‐like transcription factor in cell integrity, and newly demonstrated its role in slowdown of proliferation and survival under reduced aeration, in biofilm formation and in susceptibility to fluconazole. Our data demonstrate a tight molecular link between slowdown of proliferation during hypoxic adaptation and maintenance of cell integrity in C. neoformans and present a new role for the CRZ1 family of transcription factors in fungi. The exact positioning of this protein in cryptococcal signalling cascades remains to be clarified. Support or Funding Information This work was partially supported by Grants‐in‐Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan and Cooperative Research Program of Medical Mycology Research Center, Chiba University. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .