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

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. However, its underlying mechanism remains elusive. Here, we show that an Hsp90 co-chaperone NudC-like protein 2 (NudCL2) regulates cytokinesis by stabilizing regulator of chromosome condensation 2 (RCC2) in mammalian cells. NudCL2 co-localizes with RCC2 at the midbody and is required for RCC2 stabilization. Either NudCL2 knockout (KO) or RCC2 depletion causes similar phenotypes, including cytokinesis failure, midbody disorganization, and multinucleation. Ectopic expression of RCC2 effectively reverses the cytokinesis defect induced by NudCL2 KO. Furthermore, Hsp90 is also found to co-localize with NudCL2 at the midbody and is involved in NudCL2-mediated RCC2 stability and cytokinesis. Interestingly, our results reveal that the mRNA and newly synthesized peptides of RCC2 accumulate at the midbody. Loss of NudCL2 decreases the nascent RCC2, but not RCC2 mRNA, at the midbody. Taken together, our data provide a previously undescribed mechanism showing that NudCL2/Hsp90/RCC2 pathway is essential for cytokinesis at the midbody.