Mammalian Polo-like Kinase 1 (Plk1) Promotes Proper Chromosome Segregation by Phosphorylating and Delocalizing the PBIP1·CENP-Q Complex from Kinetochores

Park, Chi Hoon; Park, Jung Eun; Kim, Tae Sung; Yong, Kang; Soung, Nak-Kyun; Zhou, Ming; Kim, Nam Hyung; Bang, Jeong Kyu; Lee, Kyung S.

doi:10.1074/jbc.m114.623546

Cited by 19 publications

(15 citation statements)

References 26 publications

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“…While the expression of CENP-A peaked ~4h (G2 phase) after release from cell cycle synchronization at the G1/S boundary using a double thymidine block, PLK1 expression gradually increased until 12h to 24h (M to G1-phase; pHH3: M-phase marker) (Figure 1C). These changes in CENP-A and PLK1 abundance during cell cycle progression are consistent with previous reports (Park et al, 2015; Shelby et al, 1997). In βIRKO cells, CENP-A protein was significantly reduced and its peak expression was delayed to 6–12h; and PLK1 was virtually undetectable throughout the cell cycle (Figure 1C).…”

Section: Resultssupporting

confidence: 93%

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: Resultssupporting

confidence: 93%

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

et al. 2017

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“…At G2 and during the first half of M, Plk1 localizes to the centrosomes and promotes their maturation and separation to the opposite ends of the cell [9][10][11]. Plk1 is also a major player in mitotic spindle assembly, microtubulekinetochore attachment, and chromosome segregation [5,[12][13][14][15][16][17][18]. At the final stages of mitosis, Plk1 localizes to the spindle midzone where it serves to ensure accurate positioning of the cleavage furrow and proper cytokinesis [19,20].…”

Section: The Plk Family: Expression Localization and Cellular Functmentioning

confidence: 99%

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

Kazazian

Brashavitskaya

Zih

et al. 2015

Curr Colorectal Cancer Rep

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The five individual members of the mammalian polo-like kinase family play non-redundant roles in centriole replication and maturation, mitotic progression, cytokinesis, and the DNA damage response. In human colorectal cancer, Plk1 and Plk4 are expressed at higher levels in tumor than adjacent normal mucosa, and the degree of overexpression correlates with adverse prognosis. In colorectal cancer cell lines, suppression of Plk1 activity leads to mitotic arrest and apoptosis, while inhibition of Plk4 activity reduces tumor growth and invasion. Inhibition of Plk1 or Plk4 in mice using orally bioavailable agents reduces the growth of human colorectal cancer xenografts. On the basis of these preclinical studies, clinical trials of several different targeted anti-Plk1 agents have been undertaken in patients with advanced solid tumors, and a phase I trial of the anti-Plk4 inhibitor CFI-400945 is currently accruing. Here, we review the rationale, results, and potential limitations of Plks as therapeutic targets. Evidence from genetic mouse models suggests that Plk1, Plk2, Plk3, and Plk4 may all possess tumor suppressive activity, particularly with aging. Thus, enthusiasm for the use of targeted Plk inhibitors in cancer therapy must be tempered somewhat by the potential for development of second primary tumors in the long term.

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“…However, the PLK1 spatial regulation at kinetochores remains enigmatic due to multiple PLK1 interactions and substrates along the kinetochore–centromere axis (Lera et al, ). For example, PLK1 interacts with outer kinetochore components, including Bub1, NudC, and BubR1, as well as inner kinetochore components where it is recruited by CENP‐U/50 (Kang et al, ) and CENP‐Q (Park et al, ). PLK1 also functions at the inner centromere, 500 nm from the outer kinetochore, through binding INCENP (Goto et al, ).…”

Section: Role Of Plk1 At Centrosomes Kinetochores and Cytokinetic Mmentioning

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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Mammalian Polo-like Kinase 1 (Plk1) Promotes Proper Chromosome Segregation by Phosphorylating and Delocalizing the PBIP1·CENP-Q Complex from Kinetochores

Cited by 19 publications

References 26 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

Polo-Like Kinases in Colorectal Cancer: Potential for Targeted Therapy

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

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