Radicicol Binding to Swo1/Hsp90 and Inhibition of Growth of Specific Temperature-sensitive Cell Cycle Mutants of Fission Yeast.

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  • KI Se Won
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo Present address: Department of Biology, University of California
  • KASAHARA Koji
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo Present address: Yokohama City University
  • KWON Ho Jeong
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo Present address: Department of Bioscience and Biotechnology, Sejong University
  • ISHIGAMI Ken
    Department of Applied Biological Chemistry, Granduate School of Agriculture and Life Sciences, The University of Tokyo
  • KITAHARA Takeshi
    Department of Applied Biological Chemistry, Granduate School of Agriculture and Life Sciences, The University of Tokyo
  • BEPPU Teruhiko
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo Present address: Department of Applied Biological Sciences, College of Bioresource Sciences, Nihon University
  • YOSHIDA Minoru
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo CREST Research Project, Japan Science and Technology Corporation
  • HORINOUCHI Sueharu
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo

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A panel screening using cdc mutants of Schizosaccharomyces pombe identified radicicol as a potent growth inhibitor of certain mutants at the permissive temperature. The strains sensitive to radicicol were cdc7, cdc11, and cdc14, all of which are defective in early septum formation. Cytokinesis but not nuclear division of these mutants was inhibited by radicicol, but that of cells with the wild-type background was not. A biologically active derivative of radicicol with a biotin moiety at the C-11 position bound Swo1, an Hsp90 homologue in S. pombe. Increased Swo1 expresion partially suppressed radicicol sensitivity of cdc14 and almost completely rescued morphological abnormalities in cdc14 and cdc7 cells induced by radicicol at the permissive temperature. On the other hand, the increased Swo1 expression did not restore septum formation at the nonpermissive temperature. These results suggest that Swo1, as a molecular chaperone, plays a role in stabilizing these temperature-sensitive proteins at the permissive temperature or in activating the cytokinesis signaling cascade.

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