Radicicol binding to Swo1/Hsp90 and inhibition of growth of specific temperature-sensitive cell cycle mutants of fission yeast.
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 expression 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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Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
Kasahara
K
K
Kwon
H J
HJ
Ishigami
K
K
Kitahara
T
T
Beppu
T
T
Yoshida
M
M
Horinouchi
S
S
D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D007783:Lactones / Q000378:metabolism* / Q000494:pharmacology; D018942:Macrolides; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017027:Protein Tyrosine Phosphatases; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature
D000935:Antifungal Agents; C099502:CDC11 protein, S cerevisiae; C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins; D018841:HSP90 Heat-Shock Proteins; D007783:Lactones; D018942:Macrolides; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C091275:Swo1 protein, S pombe; C489404:CDC7 protein, S cerevisiae; C489406:cdc7 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; C035359:monorden