The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

Maerki, Sarah; Olma, Michael H.; Staubli, T.; Steigemann, Patrick; Gerlich, Daniel W.; Quadroni, Manfredo; Sumara, Izabela; Peter, Matthias

doi:10.1083/jcb.200906117

Cited by 112 publications

(130 citation statements)

References 34 publications

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“…Given that Cdc48/p97-Ufd1-Npl4 function is triggered by ubiquitylation (Ramadan et al, 2007;Ye, 2006), this implies the requirement for a specific ubiquitin ligase activity early in mitosis. Interestingly, a cullin-3-based ligase has recently been shown to ubiquitylate Aurora B and to be required for Aurora B removal from chromosomes in prometaphase (Maerki et al, 2009;Sumara et al, 2007). Moreover, cullin-3 physically interacts with Cdc48/p97 (Alexandru et al, 2008) raising the possibility that the two factors cooperate to regulate chromatin-associated Aurora B.…”

Section: Discussionmentioning

confidence: 99%

Cdc48/p97–Ufd1–Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells

Dobrynin

Popp

Romer

et al. 2011

Journal of Cell Science

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SummaryDuring exit from mitosis in Xenopus laevis egg extracts, the AAA+ ATPase Cdc48/p97 (also known as VCP in vertebrates) and its adapter Ufd1-Npl4 remove the kinase Aurora B from chromatin to allow nucleus formation. Here, we show that in HeLa cells Ufd1-Npl4 already antagonizes Aurora B on chromosomes during earlier mitotic stages and that this is crucial for proper chromosome segregation. Depletion of Ufd1-Npl4 by small interfering RNA (siRNA) caused chromosome alignment and anaphase defects resulting in missegregated chromosomes and multi-lobed nuclei. Ufd1-Npl4 depletion also led to increased levels of Aurora B on prometaphase and metaphase chromosomes. This increase was associated with higher Aurora B activity, as evidenced by the partial resistance of CENP-A phosphorylation to the Aurora B inhibitor hesperadin. Furthermore, low concentrations of hesperadin partially rescued chromosome alignment in Ufd1-depleted cells, whereas, conversely, Ufd1-depletion partially restored congression in the presence of hesperadin. These data establish Cdc48/p97-Ufd1-Npl4 as a crucial negative regulator of Aurora B early in mitosis of human somatic cells and suggest that the activity of Aurora B on chromosomes needs to be restrained to ensure faithful chromosome segregation.

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Section: Discussionmentioning

confidence: 99%

Cdc48/p97–Ufd1–Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells

Dobrynin

Popp

Romer

et al. 2011

Journal of Cell Science

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“…Is the ubiquitination of Ataxin-10 functionally coupled with cytokinesis, as the case for Aurora B? 38 These questions await further explorations.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Phosphorylation of Ataxin-10 by polo-like kinase 1 is required for cytokinesis

Li¹,

Wang²,

Hou³

et al. 2011

Cell Cycle

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“…Two mammalian CRL3s, CRL3 KLHL9/KLHL13 and CRL3 KLHL21 , ubiquitylate the Aurora B kinase, a protein required for chromosome segregation and cytokinesis. CRL3 KLHL21 attaches a single ubiquitin to Aurora B; monoubiquitylation is a nondestructive signal that, in this case, alters the subcellular localization of Aurora B instead of targeting it to the proteasome (Maerki et al 2009). The CRL3 KLHL9/KLHL13 ligase attaches a polyubiquitin chain of unknown linkage type to Aurora B, and this modification also results in a change in localization rather than degradation (Sumara et al 2007).…”

Section: Kelch Functions As An E3 Ubiquitin Ligase In Vivomentioning

confidence: 99%

Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase

2015

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The Drosophila Kelch protein is required to organize the ovarian ring canal cytoskeleton. Kelch binds and cross-links F-actin in vitro, and it also functions with Cullin 3 (Cul3) as a component of a ubiquitin E3 ligase. How these two activities contribute to cytoskeletal remodeling in vivo is not known. We used targeted mutagenesis to investigate the mechanism of Kelch function. We tested a model in which Cul3-dependent degradation of Kelch is required for its function, but we found no evidence to support this hypothesis. However, we found that mutant Kelch deficient in its ability to interact with Cul3 failed to rescue the kelch cytoskeletal defects, suggesting that ubiquitin ligase activity is the principal activity required in vivo. We also determined that the proteasome is required with Kelch to promote the ordered growth of the ring canal cytoskeleton. These results indicate that Kelch organizes the cytoskeleton in vivo by targeting a protein substrate for degradation by the proteasome.

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The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

Abstract: Selective ubiquitination of Aurora B by different Cul3 adaptors targets it at the correct time to the correct place during mitosis.

Cited by 112 publications

References 34 publications

Cdc48/p97–Ufd1–Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells

Cdc48/p97–Ufd1–Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells

Phosphorylation of Ataxin-10 by polo-like kinase 1 is required for cytokinesis

Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase

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