Designed inhibitor for nuclear localization signal of polo-like kinase 1   induces mitotic arrest

doi:10.1111/cbdd.12896

CORC > 北京大学 > 化学与分子工程学院

	Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces mitotic arrest
	Chen, Fangjin ; Zhuo, Xiaolong ; Qin, Tan ; Guo, Xiao ; Zhang, Chuanmao ; Lai, Luhua
刊名	CHEMICAL BIOLOGY & DRUG DESIGN
	2017
关键词	anticancer mitotic arrest nuclear localization signal Plk1 inhibitor polo-like kinase 1 BOX DOMAIN CANCER-THERAPY CENTROSOME MATURATION PLK1 PHOSPHORYLATION AURORA MITOSIS ENTRY
DOI	10.1111/cbdd.12896
英文摘要	Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates multiple essential steps of the cell cycle progression. Plk1 is overexpressed in multiple cancer cell lines and considered to be a prime anticancer target. Plk1 accumulates in the nucleus during S and G2 phases by its bipartite nuclear localization signal (NLS) sequence, which is crucial for Plk1 regulation during normal cell cycle progression. Here, through combined computational and experimental studies, we identified compound D110, which inhibits Plk1 kinase activity with an IC50 of 85nm and blocks the nuclear localization of Plk1 during S and G2 phases. D110-treated cancer cells were arrested at mitosis with monopolar spindle, indicating the inhibition of the Plk1 kinase activity in cell. As D110 interacts with both the ATP site and the NLS in Plk1, it demonstrates good selectivity toward Plk2 and Plk3. The strategy of simultaneously inhibiting kinase activity and its subcellular translocations offers a novel approach for selective kinase inhibitor design.; Ministry of Science and Technology of China [2010CB833705, 2012AA020308]; National Natural Science Foundation of China [91313302]; SCI(E); ARTICLE; 5; 732-740; 89
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473752]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Chen, Fangjin,Zhuo, Xiaolong,Qin, Tan,et al. Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces mitotic arrest[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2017.
APA	Chen, Fangjin,Zhuo, Xiaolong,Qin, Tan,Guo, Xiao,Zhang, Chuanmao,&Lai, Luhua.(2017).Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces mitotic arrest.CHEMICAL BIOLOGY & DRUG DESIGN.
MLA	Chen, Fangjin,et al."Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces mitotic arrest".CHEMICAL BIOLOGY & DRUG DESIGN (2017).