SUMOylation in Control of Accurate Chromosome Segregation during Mitosis

Wan, Jun; Subramonian, Divya; Zhang, Xiang Dong

doi:10.2174/138920312802430563

Cited by 47 publications

(37 citation statements)

References 160 publications

(350 reference statements)

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“…These findings suggest that cycles of SUMOylation and deSUMOylation modulate proteins in KT-directed mitotic processes that ultimately govern chromosome segregation (Wan et al, 2012).…”

Section: Introductionmentioning

confidence: 85%

“…Protein conjugation with SUMO (small ubiquitin-related modifier) peptides is a post-translational modification of growing importance in cell division (reviewed by Wan et al, 2012;Flotho and Werner, 2012;Eifler and Vertegaal, 2015). SUMO addition modifies the interaction surfaces of proteins and can modulate their interaction profile, localisation or function.…”

Section: Introductionmentioning

confidence: 99%

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Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

Gilistro

Turris

Damizia

et al. 2017

Journal of Cell Science

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Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity, and is implicated in some cancer types. RANBP2 is part of a larger complex, consisting of SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2-SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here, we address the mechanisms that regulate this localisation and how they affect kinetochore functions. Using proximity ligation assays, we find that nuclear transport receptors importin-β and CRM1 play essential roles in localising the RANBP2-SUMO-RANGAP1 complex away from, or at kinetochores, respectively. Using newly generated inducible cell lines, we show that overexpression of nuclear transport receptors affects the timing of RANBP2 localisation in opposite ways. Concomitantly, kinetochore functions are also affected, including the accumulation of SUMOconjugated topoisomerase-IIα and stability of kinetochore fibres. These results delineate a novel mechanism through which nuclear transport receptors govern the functional state of kinetochores by regulating the timely deposition of RANBP2.

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“…These findings suggest that cycles of SUMOylation and deSUMOylation modulate proteins in KT-directed mitotic processes that ultimately govern chromosome segregation (Wan et al, 2012).…”

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

Gilistro

Turris

Damizia

et al. 2017

Journal of Cell Science

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“…14,[17][18][19] Several genetic studies in model organisms and cell biological studies show that SUMOylation is a critical modification in dictating proper chromosome segregation during mitosis. 20 For instance, SUMO protease, SENP2 overexpression has been demonstrated to cause mitotic defects by induction of prometaphase arrest. 21,22 Additionally, human cells lacking SUMO E3 ligase PIASy results in a prolonged metaphase.…”

Section: Introductionmentioning

confidence: 99%

SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis

Sridharan

Azuma

2016

Cell Cycle

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Polo-like kinase 1 (Plk1)-interacting checkpoint helicase (PICH) localizes at the centromere and is critical for proper chromosome segregation during mitosis. However, the precise molecular mechanism of PICH's centromeric localization and function at the centromere is not yet fully understood. Recently, using Xenopus egg extract assays, we showed that PICH is a promiscuous SUMO binding protein. To further determine the molecular consequence of PICH/SUMO interaction on PICH function, we identified 3 SUMOinteracting motifs (SIMs) on PICH and generated a SIM-deficient PICH mutant. Using the conditional expression of PICH in cells, we found distinct roles of PICH SIMs during mitosis. Although all SIMs are dispensable for PICH's localization on ultrafine anaphase DNA bridges, only SIM3 (third SIM, close to the Cterminus end of PICH) is critical for its centromeric localization. Intriguingly, the other 2 SIMs function in chromatin bridge prevention. With these results, we propose a novel SUMO-dependent regulation of PICH's function on mitotic centromeres.

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“…The results are consistent with a missegregation of MIC chromosomes during mitosis. The requirement for SUMOylation in chromosome segregation is well established for other species (48)(49)(50)(51). In budding yeast, deletion of UBC9 results in gross defects in chromosome structure and integrity as well as aberrant segregation and polyploidy (15).…”

Section: Discussionmentioning

confidence: 99%

Depletion of UBC9 Causes Nuclear Defects during the Vegetative and Sexual Life Cycles in Tetrahymena thermophila

et al. 2015

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Ubc9p is the sole E2-conjugating enzyme for SUMOylation, and its proper function is required for regulating key nuclear events such as transcription, DNA repair, and mitosis. In Tetrahymena thermophila, the genome is separated into a diploid germ line micronucleus (MIC) that divides by mitosis and a polyploid somatic macronucleus (MAC) that divides amitotically. This unusual nuclear organization provides novel opportunities for the study of SUMOylation and Ubc9p function. We identified the UBC9 gene and demonstrated that its complete deletion from both MIC and MAC genomes is lethal. Rescue of the lethal phenotype with a GFP-UBC9 fusion gene driven by a metallothionein promoter generated a cell line with CdCl 2 -dependent expression of green fluorescent protein (GFP)-Ubc9p. Depletion of Ubc9p in vegetative cells resulted in the loss of MICs, but MACs continued to divide. In contrast, expression of catalytically inactive Ubc9p resulted in the accumulation of multiple MICs. Critical roles for Ubc9p were also identified during the sexual life cycle of Tetrahymena. Cell lines that were depleted for Ubc9p did not form mating pairs and therefore could not complete any of the subsequent stages of conjugation, including meiosis and macronuclear development. Mating between cells expressing catalytically inactive Ubc9p resulted in arrest during macronuclear development, consistent with our observation that Ubc9p accumulates in the developing macronucleus. P osttranslational modification by small ubiquitin-related modifier (SUMO) is a major regulator of protein function (reviewed in references 1-5). Unlike ubiquitin, which primarily targets proteins for proteasome-mediated degradation, SUMOylation alters the intracellular localization, protein-protein interactions, or posttranslational modifications of the target (6, 7). The importance of SUMOylation is evident from its roles in the regulation of transcription, mitosis, meiosis, and DNA damage repair (2, 8-10). The SUMO protein is expressed in known eukaryotes, and many proteins required for SUMOylation, including Ubc9p, are highly conserved from protozoa to multicellular species (8). Like ubiquitin, mature SUMO proteins are activated by a heterodimeric E1-activating enzyme (9) in an ATP-dependent reaction. Subsequently, SUMO is transferred from the E1 enzyme active-site Cys to a Cys residue-linked thioester bond in the E2 enzyme known as Ubc9p (10). In the last step, SUMO is attached to the target protein through a Lys-linked isopeptide bond. In vitro, conjugation of SUMO onto substrates can be done directly by Ubc9p; in vivo, E3 ligases increase the specificity and efficiency of the reaction (11, 12).Ubc9p is the only known SUMO E2 enzyme and therefore is a key modulator of SUMOylation. Ubc9p was first described as an essential protein for mitosis in fission yeast (13). Studies of several eukaryotes highlight its importance in multiple aspects of mitosis, including the maintenance of chromosome integrity, proper chromosome segregation, cell cycle progression, kinetochore ...

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SUMOylation in Control of Accurate Chromosome Segregation during Mitosis

Cited by 47 publications

References 160 publications

Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

Importin-β and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis

Depletion of UBC9 Causes Nuclear Defects during the Vegetative and Sexual Life Cycles in Tetrahymena thermophila

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