Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells

Thomas, Y.; Cirillo, Luca; Panbianco, Costanza Viola Sofia; Martino, Lisa; Tavernier, Nicolas; Schwager, Françoise; Hove, Lucie Van; Joly, Nicolas; Santamaría, Anna; Pintard, Lionel; Gotta, Monica

doi:10.1016/j.celrep.2016.03.049

Cited by 45 publications

(63 citation statements)

References 37 publications

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“…CENP-A is phosphorylated during early mitosis by Cdk1 and this phosphorylation is required for mitotic exit (Yu et al, 2015). Cdk1 also phosphorylates SPAT-1/Bora protein, a PLK1 activator, and regulates mitotic entry (Thomas et al, 2016). Thus Cdk activity is essential for proper cell cycle progression by regulating CENP-A and PLK1 activity.…”

Section: Discussionmentioning

confidence: 99%

Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation

et al. 2017

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Summary Investigation of cell cycle kinetics in mammalian pancreatic β-cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β-cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis while knocking down CENP-A limits β-cell proliferation and survival. CENP-A deficiency in β-cells leads to impaired adaptive proliferation in response to pregnancy, acute and chronic insulin resistance, and aging in mice. Insulin-stimulated CENP-A/PLK1 protein expression is blunted in islets from patients with type 2 diabetes. These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell cycle progression as an essential component in the β-cell adaptation to delay and/or prevent progression to diabetes.

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Section: Discussionmentioning

confidence: 99%

Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation

et al. 2017

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“…33 Second, several regulatory sites on Bora have been identified as well as a very prominent phospho-shift. 7, 10, 12, 25, 34, 35, 36 Therefore, it is conceivable that the phosphorylation of these sites in Bora might have a role in creating a DDR-sensitive and -reversible docking platform for Aurora A. As recruitment of Aurora A to the Plk1/Bora complex is an important step in this process, it would be interesting to investigate which of the previously identified phosphorylation sites on Bora contribute to Aurora A recruitment or recognition of the Plk1/Bora complex, to provide more insights into the mechanism and dynamics of Plk1 activation.…”

Section: Discussionmentioning

confidence: 99%

“…7, 8, 9 Phosphorylation of Plk1 at T210 by Aurora A requires binding of the co-factor Bora. 7, 9 During G2, Plk1 and Bora form a complex, which is initiated by Cdk1 activity 10, 11, 12 and leads to initial Plk1 activation in the nucleus. 13 …”

Section: Introductionmentioning

confidence: 99%

Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora

et al. 2016

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When cells in G2 phase are challenged with DNA damage, several key mitotic regulators such as Cdk1/Cyclin B, Aurora A and Plk1 are inhibited to prevent entry into mitosis. Here we have studied how inhibition of Plk1 is established after DNA damage. Using a Förster resonance energy transfer (FRET)-based biosensor for Plk1 activity, we show that inhibition of Plk1 after DNA damage occurs with relatively slow kinetics and is entirely dependent on loss of Plk1-T210 phosphorylation. As T210 is phosphorylated by the kinase Aurora A in conjunction with its co-factor Bora, we investigated how they are affected by DNA damage. Interestingly, we find that the interaction between Bora and Plk1 remains intact during the early phases of the DNA damage response (DDR), whereas Plk1 activity is already inhibited at this stage. Expression of an Aurora A mutant that is refractory to inhibition by the DDR failed to prevent inhibition of Plk1 and loss of T210 phosphorylation, suggesting that inhibition of Plk1 may be established by perturbing recruitment of Aurora A by Bora. Indeed, expression of a fusion in which Aurora A was directly coupled to Bora prevented DNA damage-induced inhibition of Plk1 activity, as well as inhibition of T210 phosphorylation. Taken together, these data demonstrate that DNA damage affects the function of Aurora A at multiple levels: both by direct inhibition of Aurora A activity, as well as by perturbing the interaction with its co-activator Bora. We propose that the DDR targets recruitment of Aurora A to the Plk1/Bora complex to prevent activation of Plk1 during DNA damage in G2.

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“…The CDK1 kinase domain recognizes the motif Ser–Ser/Thr–Pro/X on PLK1‐binding scaffolds and is able to phosphorylate the second amino acid, known as priming, allowing for PLK1–PBD interactions (Enserink & Kolodner, ). Some of the identified scaffolds that require this priming by CDK1 are Bora, Gravin, and cenexin (Canton et al, ; Soung et al, ; Thomas et al, ). PLK1 also has the ability to phosphorylate its own scaffold, such as PBIP1 and BubR1 at the centromeres, a mechanism commonly used to maintain its localization at kinetochores (Elowe, Hümmer, Uldschmid, Li, & Nigg, ; Lee, Oh, Kang, & Park, ).…”

Section: Function Of Plk1mentioning

confidence: 99%

“…(Choi, Liu, Sze, Dai, & Qi, ; Doxsey, Steln, Evans, Calarco, & Kirschnefi, ; Fabbro et al, ; Kolobova et al, ; Zimmerman, Sillibourne, Rosa, & Doxsey, ). The recruitment of these components require activated mitotic signaling cascades involving the mitotic kinases Aurora A, polo‐like kinases (PLKs), and cyclin‐dependent kinase 1 (CDK1) to name a few (Bruinsma et al, ; Hehnly et al, ; Lee et al, ; Sanhaji et al, ; Thomas et al, ). One kinase that seems to be at the center of this process from a single cell eukaryote to a multi‐cellular vertebrate is polo‐like kinase 1 (PLK1).…”

Section: Introductionmentioning

confidence: 99%

Regulating a key mitotic regulator, polo‐like kinase 1 (PLK1)

Colicino

Hehnly

2018

Cytoskeleton

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During cell division, duplicated genetic material is separated into two distinct daughter cells. This process is essential for initial tissue formation during development and to maintain tissue integrity throughout an organism's lifetime. To ensure the efficacy and efficiency of this process, the cell employs a variety of regulatory and signaling proteins that function as mitotic regulators and checkpoint proteins. One vital mitotic regulator is polo‐like kinase 1 (PLK1), a highly conserved member of the polo‐like kinase family. Unique from its paralogues, it functions specifically during mitosis as a regulator of cell division. PLK1 is spatially and temporally enriched at three distinct subcellular locales; the mitotic centrosomes, kinetochores, and the cytokinetic midbody. These localization patterns allow PLK1 to phosphorylate specific downstream targets to regulate mitosis. In this review, we will explore how polo‐like kinases were originally discovered and diverged into the five paralogues (PLK1‐5) in mammals. We will then focus specifically on the most conserved, PLK1, where we will discuss what is known about how its activity is modulated, its role during the cell cycle, and new, innovative tools that have been developed to examine its function and interactions in cells.

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Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells

Cited by 45 publications

References 37 publications

Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation

Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation

Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora

Regulating a key mitotic regulator, polo‐like kinase 1 (PLK1)

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