Photocontrol of ATPase Avtivity of Kinesin Kif18A using Various Existing Azoboenzene Derivatives

Abstract

The shape and function of the mitotic spindle depends on the cooperation action of various kinesins. Recently, it was demonstrated that the kinesin Kif18A is a central component for the correct alignment of chromosomes at the spindle equator. BTB-1 inhibits ATPase activity of kif18A but not of other mitotic kinesins. BTB-1 is a potent inhibitor for kinesin Kif18A. In mitosis cell, inhibition of Kif18A by BTB-1 occur disorder chromosome congression and cell lead to apotosis. In vitro, BTB-1 inhibits the motility of Kif18A in a reversible manner. BTB-1 inhibits Kif18A ATPase activity in an ATP competitive manner but microtubule. BTB-1 is composed of chloro group and the nitro group and the two aromatic rings. Azobenzen is one of the photochromic molecules that change their shapes and properities drastically upon ultra-violet (UV) and visible (VIS) light irradiation. Previously, we have incorporated azobenzen derivative into functional region of ATP driven motor protein and succeeded to control microtubule dependent ATPase activity reversibly by UV-VIS light irradiation. Interestingly, BTB-1 shows structural similarity to azobenzen derivatives. In this study, we examined photo-reversible inhibitory effects of various existing azobenzen derivatives for the ATPase activity of kif18A. Cis isomer of 4-aminoazoboenzene-4-sulfonic acid induced by UV irradiation inhibited ATPase activity of Kif18A more effectively than its trans isomer. Other azobenzen derivate were also examined.This work was supported by Grant-in-Aid for Challenging Exploratory Research(23650276)from Japan Society for the Promotion of Science (JSPS).