A novel action of terpendole E on the motor activity of mitotic Kinesin Eg5.
To reveal the mechanism of mitosis, the development of M phase-specific inhibitors is an important strategy. We have been screening microbial products to find specific M phase inhibitors that do not directly target tubulins, and rediscovered terpendole E (TerE) as a novel Eg5 inhibitor. TerE did not affect microtubule integrity in interphase, but induced formation of a monoastral spindle in M phase. TerE inhibited both motor and microtubule-stimulated ATPase activities of human Eg5, but did not affect conventional kinesin from either Drosophila or bovine brain. Although terpendoles have been reported as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT), the Eg5 inhibitory activity of TerE was independent of ACAT inhibition. Taken together, we demonstrate that TerE is a novel Eg5 inhibitor isolated from a fungal strain.
Nakazawa
Junko
J
Antibiotics Laboratory, RIKEN Institute for Discovery Research, Hirosawa 2-1,Wako-shi, Saitama 351-0198, Japan.
Yajima
Junichiro
J
Usui
Takeo
T
Ueki
Masashi
M
Takatsuki
Akira
A
Imoto
Masaya
M
Toyoshima
Yoko Y
YY
Osada
Hiroyuki
H
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004926:Escherichia coli; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008677:Metaphase / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D010641:Phenotype; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D014404:Tubulin / Q000096:biosynthesis; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D004224:Diterpenes; D007211:Indoles; C088335:KIF11 protein, Xenopus; D014404:Tubulin; D029867:Xenopus Proteins; C477863:terpendole E; D002785:Sterol O-Acyltransferase; D000251:Adenosine Triphosphatases; D016547:Kinesins