Skip to Content
Merck
  • Phosphorylation of SKAP by GSK3β ensures chromosome segregation by a temporal inhibition of Kif2b activity.

Phosphorylation of SKAP by GSK3β ensures chromosome segregation by a temporal inhibition of Kif2b activity.

Scientific reports (2016-12-17)
Bo Qin, Dan Cao, Huihui Wu, Fei Mo, Hengyi Shao, Jane Chu, Michael Powell, Felix Aikhionbare, Dongmei Wang, Chuanhai Fu, Ping He, Weijun Pan, Wenwen Wang, Xing Liu, Xuebiao Yao
ABSTRACT

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent study shows SKAP is an EB1-dependent, microtubule plus-end tracking protein essential for kinetochore oscillations during mitosis. Here we show that phosphorylation of SKAP by GSK3β regulates Kif2b depolymerase activity by competing Kif2b for microtubule plus-end binding. SKAP is a bona fide substrate of GSK3β in vitro and the phosphorylation is essential for an accurate kinetochore-microtubule attachment in cells. The GSK3β-elicited phosphorylation sites were mapped by mass spectrometry and the phosphomimetic mutant of SKAP can rescue the phenotype of chromosome missegregation in SKAP-suppressed cells. Importantly, GSK3β-elicited phosphorylation promotes SKAP binding to Kif2b to regulate its depolymerase activity at the microtubule plus-ends. Based on those findings, we reason that GSK3β-SKAP-Kif2b signaling axis constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human KIF2B