TY - JOUR
T1 - NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody
AU - Xu, Xiaoyang
AU - Huang, Yuliang
AU - Yang, Feng
AU - Sun, Xiaoxia
AU - Lin, Rijin
AU - Feng, Jiaxing
AU - Yang, Mingyang
AU - Shao, Jiaqi
AU - Liu, Xiaoqi
AU - Zhou, Tianhua
AU - Xie, Shanshan
AU - Yang, Yuehong
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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 successful 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 mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation, 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.
AB - 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 successful 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 mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation, 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.
KW - Hsp90
KW - NudCL2
KW - RCC2
KW - cytokinesis
KW - midbody
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U2 - 10.1093/procel/pwae025
DO - 10.1093/procel/pwae025
M3 - Article
C2 - 38801297
AN - SCOPUS:85205525858
SN - 1674-800X
VL - 15
SP - 766
EP - 782
JO - Protein and Cell
JF - Protein and Cell
IS - 10
ER -