NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody  

作　　者：Xiaoyang Xu Yuliang Huang Feng Yang Xiaoxia Sun Rijin Lin Jiaxing Feng Mingyang Yang Jiaqi Shao Xiaoqi Liu Tianhua Zhou Shanshan Xie Yuehong Yang 

机构地区：[1]Department of Cell Biology,Institute of Gastroenterology of the Second Affliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China [2]Research Center for Children's Health and Innovation,Binjiang Institute of Zhejiang University,Hangzhou 310053,China [3]Department of Biochemistry,Purdue University,West Lafayette,IN 47907,United States [4]Cancer Center,Zhejiang University,Hangzhou 310058,China [5]Center for RNA Medicine,International Institutes of Medicine,the Fourth Affliated Hospital of Zhejiang University School of Medicine,Yiwu 322000,China [6]Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China

出　　处：《Protein & Cell》2024年第10期766-782,共17页蛋白质与细胞（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.32070709,32270771,and U21A20197);the National Key Research and Development Program of China(Nos.2019YFA0802202);the Higher Education Discipline Innovation Project(also known as the111 Project)(Nos.B13026).

摘　　要：Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells.Midbody,a protein-dense organelle that forms at the intercellular bridge,is indispensable for success-ful cytokinesis.However,the regulatory mechanism of cytokinesis at the midbody still remains elusive.Here,we unveil a critical role for NudC-like protein 2(NudCL2),a co-chaperone of heat shock protein 90(Hsp90),in cytokinesis regulation by stabilizing regulator of chromosome condensation 2(RCC2)at the midbody in mam-malian cells.NudCL2 localizes at the midbody,and its downregulation results in cytokinesis failure,multinu-cleation,and midbody disorganization.Using iTRAQ-based quantitative proteomic analysis,we find that RCC2 levels are decreased in NudCL2 knockout(KO)cells.Moreover,Hsp90 forms a complex with NudCL2 to stabilize RCC2,which is essential for cytokinesis.RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells.Importantly,ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion,but not vice versa.Together,our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.

关 键 词：CYTOKINESIS MIDBODY NudCL2 HSP90 RCC2 

分 类 号：Q253[生物学—细胞生物学]