Plk1 Self-Organization and Priming Phosphorylation of HsCYK-4 at the Spindle Midzone Regulate the Onset of Division in Human Cells

Burkard, Mark E.; Maciejowski, John; Rodríguez-Bravo, Verónica; Repka, Michael C.; Lowery, Drew M.; Clauser, Karl R.; Zhang, Chao; Shokat, Kevan M.; Carr, Steven A.; Yaffe, Michael B.; Jallepalli, Prasad V.

doi:10.1371/journal.pbio.1000111

Cited by 175 publications

(245 citation statements)

References 71 publications

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“…3) (Lee et al 2004;Yuce et al 2005;Zhao and Fang 2005;Kamijo et al 2006;Su et al 2011). The interaction between ECT2 and RacGAP1 requires phosphorylation of RacGAP1 by Polo-like kinase 1 (Plk1) in anaphase/telophase and is, instead, inhibited by Cdk1-mediated phosphorylation of ECT2 in metaphase (Yuce et al 2005;Burkard et al 2007Burkard et al , 2009Petronczki et al 2007;Wolfe et al 2009). Phosphorylation of the ECT2 carboxyterminal polybasic cluster region by Cdk1 also prevents the association of this GEF with the plasma membrane before anaphase onset (Su et al 2011).…”

Section: Cleavage Furrow Ingression: Actomyosin Filaments Take Centermentioning

confidence: 99%

Cytokinesis in Animal Cells

D’Avino

Giansanti

Petronczki

2015

Cold Spring Harb Perspect Biol

182

226

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Section: Cleavage Furrow Ingression: Actomyosin Filaments Take Centermentioning

confidence: 99%

Cytokinesis in Animal Cells

D’Avino

Giansanti

Petronczki

2015

Cold Spring Harb Perspect Biol

182

226

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“…In prometaphase, PLK1 is required for the generation of stable kinetochoremicrotubule attachments (7)(8)(9)(10). PLK1 also promotes dissociation of cohesin from chromosome arms in prophase and prometaphase by phosphorylating cohesin's STAG2 subunit (11)(12)(13)(14), as well as multiple aspects of cytokinesis by phosphorylating activators and effectors of RhoA (1,15).…”

mentioning

confidence: 99%

Quantitative Phospho-proteomics to Investigate the Polo-like Kinase 1-Dependent Phospho-proteome

Grosstessner-Hain

Hegemann

Novatchkova

et al. 2011

Molecular & Cellular Proteomics

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Polo-like kinase 1 (PLK1) is a key regulator of mitotic progression and cell division, and small molecule inhibitors of PLK1 are undergoing clinical trials to evaluate their utility in cancer therapy. Despite this importance, current knowledge about the identity of PLK1 substrates is limited. Here we present the results of a proteome-wide analysis of PLK1-regulated phosphorylation sites in mitotic human cells. We compared phosphorylation sites in HeLa cells that were or were not treated with the PLK1-inhibitor BI 4834, by labeling peptides via methyl esterification, fractionation of peptides by strong cation exchange chromatography, and phosphopeptide enrichment via immobilized metal affinity chromatography. Analysis by quantitative mass spectrometry identified 4070 unique mitotic phosphorylation sites on 2069 proteins. Of these, 401 proteins contained one or multiple phosphorylation sites whose abundance was decreased by PLK1 inhibition. These include proteins implicated in PLK1-regulated processes such as DNA damage, mitotic spindle formation, spindle assembly checkpoint signaling, and chromosome segregation, but also numerous proteins that were not suspected to be regulated by

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“…Activation of RhoA during anaphase also requires activating phosphorylations, including phosphorylation of the centralspindlin subunit Cyk4 by Plk1. Phospho-Cyk4 binds to the Rho GDP-GTP exchange factor (GEF) Ect2 (Burkard et al 2009;Wolfe et al 2009), relieving its autoinhibition.…”

Section: Temporal Control In Metazoamentioning

confidence: 99%

“…Centralspindlin activates the RhoGEF Ect2, which activates RhoA at the plasma membrane; thus, these interactions could direct positioning of the division plane (Fig. 1B,C) (Yüce et al 2005;Burkard et al 2009;Zhang and Glotzer 2015).…”

Section: Spindle-dependent Division-plane Positioning In Metazoamentioning

confidence: 99%

Cytokinesis in Metazoa and Fungi

Glotzer

2016

Cold Spring Harb Perspect Biol

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SUMMARYCell division-cytokinesis-involves large-scale rearrangements of the entire cell. Primarily driven by cytoskeletal proteins, cytokinesis also depends on topological rearrangements of the plasma membrane, which are coordinated with nuclear division in both space and time. Despite the fundamental nature of the process, different types of eukaryotic cells show variations in both the structural mechanisms of cytokinesis and the regulatory controls. In animal cells and fungi, a contractile actomyosin-based structure plays a central, albeit flexible, role. Here, the underlying molecular mechanisms are summarized and integrated and common themes are highlighted.

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Plk1 Self-Organization and Priming Phosphorylation of HsCYK-4 at the Spindle Midzone Regulate the Onset of Division in Human Cells

Abstract: Self-regulated movement of Polo-like kinase 1 to the midzone of the mitotic spindle initiates a local signaling cascade that activates the cell division machinery at the cell's equator.

Cited by 175 publications

References 71 publications

Cytokinesis in Animal Cells

Cytokinesis in Animal Cells

Quantitative Phospho-proteomics to Investigate the Polo-like Kinase 1-Dependent Phospho-proteome

Cytokinesis in Metazoa and Fungi

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