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 succe...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.展开更多
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).
文摘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.
