Hsp90 interaction with Cdc2 and Plo1 kinases contributes to actomyosin ring condensation in fission yeast

Santino, Andrea; Jiménez, Juan; Garzón, Andrés

doi:10.1007/s00294-012-0376-4

“…They include such putative targets as Hsp90, Wos2, Rad24, and Clp1/Flp1. Hsp90 and its cochaperone Wos2 regulate cell cycle progression and actomyosin ring assembly during cytokinesis , while Rad24 and Cdc14 regulate G2/M transition . It is also possible that some PP2A targets responsible for its ability to regulate cell cycle and morphogenesis might be below the detection threshold of the 2D‐DIGE and MS analysis techniques used in our work.…”

Section: Discussionmentioning

confidence: 99%

Proteome‐wide search for PP2A substrates in fission yeast

Bernal

¹

,

Zhurinsky

²

,

Iglesias-Romero

³

et al. 2014

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PP2A (protein phosphatase 2A) is a major phosphatase in eukaryotic cells that plays an essential role in many processes. PP2A mutations in Schizosaccharomyces pombe result in defects of cell cycle control, cytokinesis and morphogenesis. Which PP2A substrates are responsible for these changes is not known. In this work, we searched for PP2A substrates in S. pombe using two approaches, 2D-DIGE analysis of PP2A complex mutants and identification of PP2A interacting proteins. In both cases, we used MS to identify proteins of interest. In the DIGE experiment, we compared proteomes of wild-type S. pombe, deletion of pta2, the phosphoactivator of the PP2A catalytic subunit, and pab1-4, a mutant of B-type PP2A regulatory subunit. A total of 1742 protein spots were reproducibly resolved by 2D-DIGE and 51 spots demonstrated significant changes between PP2A mutants and the wild-type control. MS analysis of these spots identified 27 proteins that include key regulators of glycerol synthesis, carbon metabolism, amino acid biosyntesis, vitamin production, and protein folding. Importantly, we independently identified a subset of these proteins as PP2A binding partners by affinity precipitation, suggesting they may be direct targets of PP2A. We have validated our approach by demonstrating that phosphorylation of Gpd1, a key enzyme in glycerol biogenesis, is regulated by PP2A and that ability of cells to respond to osmotic stress by synthesizing glycerol is compromised in the PP2A mutants. Our work contributes to a better understanding of PP2A function and identifies potential PP2A substrates.

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“…Inhibition of Hsp90 function results in the cell cycle arrest in G2/M 62 . Recently, Hsp90 was found to play a role in cytokinesis in fission yeast and African trypanosomes 63,64 . However, whether Hsp90 is required for cytokinesis in mammalian cells is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

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

Xu

¹

,

Huang

²

,

Yu

³

et al. 2023

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0

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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.

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“…Inhibition of Hsp90 function results in the cell cycle arrest in G2/M 59 . Recently, Hsp90 was found to play a role in cytokinesis in fission yeast and African trypanosomes 60,61 . However, whether Hsp90 is required for cytokinesis in mammalian cells is largely unknown.…”

Section: Ectopic Expression Of Rcc2 Is Able To Reverse the Cytokinesi...mentioning

confidence: 99%

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

Xu

¹

,

Huang

²

,

Yu

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

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.

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Hsp90 interaction with Cdc2 and Plo1 kinases contributes to actomyosin ring condensation in fission yeast

Cited by 5 publications

References 69 publications

Proteome‐wide search for PP2A substrates in fission yeast

Proteome‐wide search for PP2A substrates in fission yeast

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

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

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