Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by <scp>PP</scp>1 and <scp>PP</scp>2A

Holder, James; Poser, Elena; Barr, Francis A.

doi:10.1002/1873-3468.13595

Cited by 69 publications

(67 citation statements)

References 160 publications

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“…We would expand upon this by suggesting that prior destruction of CCNA2 ensures that proteolysis of CCNB1 creates a state of low CDK activity, fundamentally different to G2 which is governed by CDK1-CCNA2 activity. This inherent asymmetry would drive the cell cycle forward into anaphase rather than reverting back to a G2-like state (Holder et al, 2019). Consistent with this, expression of a non-degradable form of CCNA2 traps cells in anaphase A and does not permit further progression through mitotic exit (Geley et al, 2001).…”

Section: Ordered Proteolysis Of Cyclins During Mitosis and Mitotic Exitmentioning

confidence: 83%

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

Holder

Mohammed

Barr

2020

eLife

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APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution proteomics, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid proteolysis of cyclin B, securin and geminin at the metaphase-anaphase transition, followed by slow proteolysis of other substrates. Dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent categories with unique sequence motifs. We conclude that dephosphorylation initiated by selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit.

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Section: Ordered Proteolysis Of Cyclins During Mitosis and Mitotic Exitmentioning

confidence: 83%

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

Holder

Mohammed

Barr

2020

eLife

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“…In addition to the APC/C, another important enzyme for mitotic exit is PP2A-B55 (Holder et al, 2019). We previously conducted a maternal-effect genetic screen for enhancers of mutations in tws, which encodes the B55 regulatory subunit of PP2A in Drosophila.…”

Section: Cycb3 Functions Upstream Of the Apc/c And Collaborates With mentioning

confidence: 99%

“…Progression through these initial phases requires multiple phosphorylation events of various protein substrates by mitotic kinases including Cyclin-Dependent Kinases (CDKs) activated by their mitotic cyclin partners (Morgan, 2007). M-phase completion from this point (mitotic exit) requires the degradation of mitotic cyclins, and the dephosphorylation of several mitotic phosphoproteins by phosphatases including Protein Phosphatase 2A (PP2A) (Holder et al, 2019). Mitotic exit begins with the segregation of chromosomes in anaphase.…”

Section: Introductionmentioning

confidence: 99%

Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis

Garrido

Bourouh

Bonneil

et al. 2020

Preprint

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In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its Cdc20 co-activator. The identity of the kinase(s) responsible for APC/C activation in vivo is unclear. Cyclin B3 is required for meiotic anaphase in flies, worms and vertebrates, but whether it activates the APC/C is unclear. We found that Drosophila Cyclin B3 (CycB3) collaborates with PP2A-B55/Tws in embryonic development, indicating that CycB3 also promotes anaphase in mitosis. Moreover, CycB3 promotes APC/C activity and anaphase in cells in culture. We show that CycB3 physically associates with the APC/C, is required for phosphorylation of APC3, and promotes APC/C association with its co-activators. We propose that CycB3-Cdk1 directly phosphorylates the APC/C to activate it in both meiosis and mitosis.

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“…Upon mitotic exit, several phosphatases promote the inactivation of mitotic kinases of the Aurora family, polo-like kinase 1 (PLK1) and the cyclin dependent kinase 1 (CDK1) [5,6]. They also mediate Depletion of not only VPS72 but also H2A.Z impairs chromatin structure as well as compactness and results in malformed nuclear envelopes.…”

Section: Introductionmentioning

confidence: 99%

VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

Moreno-Andrés

Yokoyama

Scheufen

et al. 2020

Cells

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The eukaryotic nucleus remodels extensively during mitosis. Upon mitotic entry, the nuclear envelope breaks down and chromosomes condense into rod-shaped bodies, which are captured by the spindle apparatus and segregated during anaphase. Through telophase, chromosomes decondense and the nuclear envelope reassembles, leading to a functional interphase nucleus. While the molecular processes occurring in early mitosis are intensively investigated, our knowledge about molecular mechanisms of nuclear reassembly is rather limited. Using cell free and cellular assays, we identify the histone variant H2A.Z and its chaperone VPS72/YL1 as important factors for reassembly of a functional nucleus after mitosis. Live-cell imaging shows that siRNA-mediated downregulation of VPS72 extends the telophase in HeLa cells. In vitro, depletion of VPS72 or H2A.Z results in malformed and nonfunctional nuclei. VPS72 is part of two chromatin-remodeling complexes, SRCAP and EP400. Dissecting the mechanism of nuclear reformation using cell-free assays, we, however, show that VPS72 functions outside of the SRCAP and EP400 remodeling complexes to deposit H2A.Z, which in turn is crucial for formation of a functional nucleus.

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Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

Cited by 69 publications

References 160 publications

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis

VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis

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