Studies on regulatory mechanism for cell migration based on chemical genetics

UTKO1是由Watanabe教授（东京大学）合成的。我们利用化学遗传学方法探索了UTKO1的作用模式。我们发现UTKO1通过抑制Rac1激活来抑制egf诱导的细胞迁移。为了确定UTKO1的分子靶点，Watanabe教授合成了生物素化的UTKO1，并将其作为探针获得UTKO1的靶蛋白。结果，14-3-3ζ被确定为UTKO1的功能靶蛋白，因为sirna介导的14-3-3ζ表达沉默抑制了egf诱导的细胞迁移和Rac1激活。这些结果表明，在egf诱导的细胞迁移过程中，14-3-3ζ会作用于Rac1激活的上游，而UTKO1抑制细胞迁移可能是由于14-3-3ζ功能的取消。

UTKO1 was synthesized as a derivative of moverastin by Prof. Watanabe (Univ. Tokyo). We explored the mode of action of UTKO1 by using a chemical genetic approach. We found that UTKO1 inhibited EGF-induced cell migration by inhibiting Rac1 activation. To identify the molecular target of UTKO1, biotinylated UTKO1 was synthesized by Prof. Watanabe, and was used as the probe to obtain a target protein of UTKO1. As a result, 14-3-3ζ was identified as the functional target protein of UTKO1, because siRNA-mediated silencing of 14-3-3ζ expression suppressed both EGF-induced cell migration and Rac1 activation. These results suggest that 14-3-3ζ would act upstream of Rac1 activation in the process of EGF-induced cell migration, and UTKO1 inhibited cell migration possibly due to the abrogation of 14-3-3ζ function.