Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

Emanuele, Michael J.; Lan, Weijie; Jwa, Miri; Miller, Stephanie A.; Chan, Chung Chow; Stukenberg, P. Todd

doi:10.1083/jcb.200710019

Cited by 141 publications

(161 citation statements)

References 47 publications

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“…Thus, one may envision that the attachment of the SUMO moiety to Borealin may provide a centromeric docking site for a yet to be identified SIMcontaining binding partner. Indeed, it was shown that the CPC constitutes one of the most upstream components of centromere/kinetochore assembly (Vigneron et al, 2004;Liu et al, 2006;Emanuele et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

Klein¹,

Haindl

Nigg³

et al. 2009

MBoC

111

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The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway.

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Section: Discussionmentioning

confidence: 99%

RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

Klein¹,

Haindl

Nigg³

et al. 2009

MBoC

111

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“…In Xenopus cell-free extracts, inhibition of Aurora B kinase activity causes loss of Ndc80/Hec1 from kinetochores (Emanuele et al, 2008). However, upon depletion of Seh1 both aligned and unaligned chromosomes had strong Hec1 signals marking the kinetochores ( Figure 3E), indicating that this critical kinetochore component is still targeted properly after Seh1 depletion despite the loss of Aurora B targeting.…”

Section: Seh1 Regulates Localization Of the Cpc Complex And Is Requirmentioning

confidence: 98%

The Nup107-160 Nucleoporin Complex Promotes Mitotic Events via Control of the Localization State of the Chromosome Passenger Complex

Platani

Santarella-Mellwig

Posch

et al. 2009

MBoC

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The human Nup107-160 nucleoporin complex plays a major role in formation of the nuclear pore complex and is localized to kinetochores in mitosis. Here we report that Seh1, a component of the Nup107-160 complex, functions in chromosome alignment and segregation by regulating the centromeric localization of Aurora B and other chromosome passenger complex proteins. Localization of CENP-E is not affected by Seh1 depletion and analysis by electron microscopy showed that microtubule kinetochore attachments are intact. Seh1-depleted cells show impaired Aurora B localization, which results in severe defects in biorientation and organization of the spindle midzone and midbody. Our results indicate that a major function of the Nup107 complex in mitosis is to ensure the proper localization of the CPC at the centromere. INTRODUCTIONThe nuclear envelope (NE) forms the interface between the nucleus and the cytoplasm of the interphase eukaryotic cell and is essential to maintain the unique identity of each compartment. Transport between the two compartments takes place via the nuclear pore complexes (NPCs) of which there are several thousand in vertebrate somatic cells (Allen et al., 2000;Conti and Izaurralde, 2001). Each NPC contains multiple subunits of ϳ30 proteins called nucleoporins (Nups;Cronshaw et al., 2002). In higher eukaryotes NPCs are stable throughout interphase (Daigle et al., 2001), but during mitosis both the nuclear envelope and NPC undergo major structural reorganization. Starting early in prometaphase, breakdown of the nuclear envelope occurs, including disassembly of the nuclear lamina and NPCs. The nuclear envelope membrane proteins and the transmembrane nucleoporins relocalize to the endoplasmic reticulum (ER), whereas the rest of the nuclear envelope and NPC components become distributed throughout the mitotic cytoplasm (Antonin et al., 2008).During mitosis, two complete sets of chromosomes are delivered to a pair of daughter cells. Segregation of each sister chromatid pair is achieved by a highly orchestrated process that requires attachment of the sister kinetochores of each chromosome to microtubules emanating from opposite spindle poles. Kinetochores are protein structures that assemble on chromosome regions known as centromeres and mediate microtubule attachment, mitotic checkpoint signaling, and force generation (Maiato et al., 2004;Tanaka et al., 2005;Cheeseman and Desai, 2008). Electron microscopy (EM) has provided information regarding the structure of vertebrate kinetochores and has led to the division of kinetochores into three distinct regions: the inner kinetochore that associates with chromatin, the outer kinetochore that interacts with spindle microtubules, and the less dense middle kinetochore region (McEwen et al., 2007). Multiple different MT-associated proteins function at kinetochores to form a core attachment site between kinetochore and MTs, with the KMN network (KNL-1/Mis12/NDC80 complex) being the major structural component (Cheeseman et al., 2006). Functional analysis of the NDC8...

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“…In addition to regulation of Cdk1 substrates, PP1 and PP2A have also been shown to antagonize the action of Plk1, Aurora, and other mitotic kinases (6,7). For example, it has been shown that PP1 opposes the mitotic function of Aurora B at various subcellular sites, leading to delicate control of the spatial gradient of Aurora B substrate phosphorylation (17)(18)(19). Obviously, the vast content and complex pattern of protein phosphorylation in mitosis can be much better understood with identification of various phosphatase complexes involved in M-phase progression and delineation of molecular mechanisms through which these mitotic phosphatases are regulated.…”

mentioning

confidence: 99%

Phosphatase 1 Nuclear Targeting Subunit Is an Essential Regulator of M-phase Entry, Maintenance, and Exit

Fisher

Wei

Peng

2014

Journal of Biological Chemistry

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Background: Mitotic progression is regulated by reversible protein phosphorylation involving kinases and phosphatases. Results: Pnuts functions as a master regulator of mitosis by modulating PP1; Pnuts expression peaks in mitosis and is degraded at mitotic exit. Conclusion: This study reveals the function and regulation of a new and essential mitotic regulator. Significance: This study improves our understanding of M-phase regulation.

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Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

Cited by 141 publications

References 47 publications

RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

The Nup107-160 Nucleoporin Complex Promotes Mitotic Events via Control of the Localization State of the Chromosome Passenger Complex

Phosphatase 1 Nuclear Targeting Subunit Is an Essential Regulator of M-phase Entry, Maintenance, and Exit

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