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Towards Understanding Cell Cycle Regulation in the Pathogenic Cryptococcus neoformans and Saccharomyces cerevisiae
Author(s) -
Kawamoto Susumu,
Virtudazo Eric,
Ohkusu Misako,
Suganami Akiko,
Tamura Yutaka
Publication year - 2016
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.30.1_supplement.638.4
Subject(s) - cryptococcus neoformans , saccharomyces cerevisiae , cyclin dependent kinase 1 , cell cycle , biology , cyclin , microbiology and biotechnology , in silico , yeast , genetics , cell , gene
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 ( S. 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. Only a single Cdk1‐related G1 and G1/S cyclin homologue was found in the genome sequence of C. neoformans and was designated CnCln1. Surprisingly, CnCln1 was not only able to complement the function of the G1 cyclins of S. cerevisiae , such as ScCln3, but also the G1/S cyclins of S. cerevisiae , such as ScCln1 and ScCln2. Our in silico analysis demonstrated that the CnCln1/ScCdk1 complex was more stable than any of S. cerevisiae cyclins (ScCln1, ScCln2, ScCln3) and ScCdk1 complexes. These results are consistent with in vitro analysis that has revealed the flexible functional capacity of CnCln1 as a Cdk1‐related G1 and G1/S cyclin of S. cerevisiae . On the other hand, Cln1 and Cln2, G1/S cyclins of S. cerevisiae , oscillate during the cell cycle, rising in late G1 and falling in early S phase. We have been tried to elucidate the structure basis of the functional distinction between Cln1 and Cln2. We performed in silico simulations: construction and evaluation of three dimensional structures of Cln1‐Cdc28 and Cln2‐Cdc28 complexes. Our in silico simulations suggested that the interaction of Cln1 and Cln2 with Cdc28 were in the two distinct situations, designated as flip and flop conformation, at the extra amino acid region in the cyclin box of Cln1 and Cln2. We speculated the trigger of this flip‐flop conversion of the extra amino acid region in the cyclin box of Cln1‐Cdc28 and Cln2‐Cdc28 might be regulated by the ubiquitination of the sequences rich in Pro (P), Glu (E), Ser (S) and Thr (T), so‐called PEST motifs, in Cln1 and Cln2. Furthermore, we presumed that the functional superiority between Cln1 and Cln2 in the G1/S phase of S. cerevisiae might be controlled by flip‐flop conversion and ubiquitin‐proteasome pathway. 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.