BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association t

BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on

capture of spindle microtubules

Yuejia Huang;Yin Zhang;Jiancun Zhang;Zhihong Yang;Xu Liu;Zhenye Yang;Jianye Zang;Maikun

Teng;Zhiyong

Wang;Ke

Ruan;Xia

Ding;Lin

Lin;Lin

Li;Don

W.Cleveland;Rongguang Zhang;Xuebiao Yao;Xing Liu;Sheng Ye;Phil Y.Yao;Wenwen Wang;Fengrui Yang;Xinjiao Gao;Junying Li

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2019(029)007

【摘要】Error-free mitosis depends on accurate chromosome attachment to spindle microtubules,powered congression of those chromosomes,their segregation in anaphase,and assembly of a spindle midzone at mitotic exit.The centromere-associated kinesin motor CENP-E,whose binding partner is BubR1,has been implicated in congression of misaligned chromosomes and the transition from lateral kinetochore-microtubule association to end-on capture.Although previously proposed to be a pseudokinase,here we report the structure of the kinase domain of Drosophila melanogaster BubR1,revealing its folding into a conformation predicted to be catalytically active.BubR1 is shown to be a bona fide kinase whose phosphorylation of CENP-E switches it from a laterally attached microtubule motor to a plus-end microtubule tip tracker.Computational modeling is used to identify bubristatin as a