Abstract
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.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1093/procel/pwae025
Funding Information
This study was 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), and the Higher Education Discipline Innovation Project (also known as the111 Project) (Nos. B13026).
Repository Citation
Xu, Xiaoyang; Huang, Yuliang; Yang, Feng; Sun, Xiaoxia; Lin, Rijin; Feng, Jiaxing; Yang, Mingyang; Shao, Jiaqi; Liu, Xiaoqi; Zhou, Tianhua; Xie, Shanshan; and Yang, Yuehong, "NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody" (2024). Markey Cancer Center Faculty Publications. 268.
https://uknowledge.uky.edu/markey_facpub/268
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Notes/Citation Information
© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https:// creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.