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.

中文翻译：

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NudCL2 是通过在中体用 Hsp90 稳定 RCC2 来实现胞质分裂所必需的。


胞质分裂是将细胞质成分和复制的细胞核忠实地分裂成两个子细胞所必需的。中间体是在细胞间桥上形成的蛋白质致密细胞器，对于胞质分裂的成功是必不可少的。然而，中间体胞质分裂的调节机制仍然难以捉摸。在这里，我们揭示了 NudC 样蛋白 2 （NudCL2） 的关键作用，NudCL2 是热休克蛋白 90 （Hsp90） 的共伴侣，通过稳定哺乳动物细胞中体的染色体缩合调节因子 2 （RCC2） 在胞质分裂调节中的作用。NudCL2 定位于中体，其下调导致胞质分裂失败、多核化和中体紊乱。使用基于 iTRAQ 的定量蛋白质组学分析，我们发现 NudCL2 敲除 （KO） 细胞中的 RCC2 水平降低。此外，Hsp90 与 NudCL2 形成复合物以稳定 RCC2，这对胞质分裂至关重要。RCC2 耗竭反映了在 NudCL2 下调细胞中观察到的表型。重要的是，RCC2 的异位表达挽救了 NudCL2 缺失诱导的胞质分裂缺陷，但反之则不然。总之，我们的数据揭示了 NudCL2/Hsp90/RCC2 通路在中体胞质分裂中的重要性。