Radicicol binding to Swo1/Hsp90 and inhibition of growth of specific temperature-sensitive cell cycle mutants of fission yeast

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2001-11, Vol.65 (11), p.2528-2534
• Main Authors: Ki, S.W. (Tokyo Univ. (Japan)), Kasahara, K, Kwon, H.J, Ishigami, K, Kitahara, T, Beppu, T, Yoshida, M, Horinouchi, S
• Format: Article
• Language: English
• Subjects: Antifungal Agents - metabolism; Antifungal Agents - pharmacology; Biological and medical sciences; Biotechnology; cdc mutant; CELL CYCLE; Cell Cycle Proteins - genetics; Cell Division - drug effects; Cytoskeletal Proteins; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Genes, Fungal; GROWTH; heat-shock protein; HSP90 Heat-Shock Proteins - metabolism; INHIBITION; Lactones - metabolism; Lactones - pharmacology; Macrolides; MUTANTS; Mutation; Protein Tyrosine Phosphatases; Protein-Serine-Threonine Kinases - genetics; radicicol; Saccharomyces cerevisiae Proteins; Schizosaccharomyces - drug effects; Schizosaccharomyces - genetics; Schizosaccharomyces - growth & development; Schizosaccharomyces - metabolism; SCHIZOSACCHAROMYCES POMBE; Schizosaccharomyces pombe Proteins; septum formation; TEMPERATURE
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.65.2528

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 cdc 7, 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 expression partially suppressed radicicol sensitivity of cdc 14 and almost completely rescued morphological abnormalities in cdc14 and cdc 7 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.