CLIP-170 is required to recruit PLK1 to kinetochores during early mitosis for chromosome alignment

Amin, Mohammed A.; Itoh, Go; Iemura, Kenji; Ikeda, Masanori; Tanaka, Kozo

doi:10.1242/jcs.150755

Cited by 31 publications

(34 citation statements)

References 42 publications

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“…CLIP-170 localized to kinetochores in prometaphase, which was decreased in metaphase ( Fig. S2), as reported previously [6,16,17,19]. It is known that kinetochore localization of CLIP-170 depends on dynactin [10,11,16].…”

Section: Resultssupporting

confidence: 87%

CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

2015

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Edited by Michael R. Bubb Keywords:Cytoplasmic linker protein-170 Dynein Chromosome alignment Kinetochore Microtubule Mitosis a b s t r a c tThe cytoplasmic linker protein (CLIP)-170 localizes to kinetochores and is suggested to function in stable attachment of kinetochores to microtubule ends. Here we show that defects in kinetochoremicrotubule attachment and chromosome alignment in CLIP-170-depleted cells were rescued by co-depletion of p150glued, a dynactin subunit required for kinetochore localization of CLIP-170. CLIP-170 recruited p150glued to microtubule ends. Kinetochore localization at microtubule ends was perturbed by CLIP-170 depletion, which was rescued by co-depleting p150glued. Our results imply that CLIP-170 tethers kinetochores to microtubule ends against the dynein-mediated poleward force to slide kinetochores along microtubules, facilitating the stable kinetochore attachment to microtubules.

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Section: Resultssupporting

confidence: 87%

CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

2015

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“…Thus, MT binding affinity increases in response to the recruitment of outer KT components, such as motor proteins, including dynein and Cenp-E, or MT plus end-binding proteins, including EB1, Clip-170, Ska complex, and Cenp-F. Plk1 is known to be a KT regulator because it localizes to mitotic structures, such as the centrosome, spindle, and KTs, and controls the localization of several KT-associated proteins, such as Hec1, Cdc20, Mad2, and Cenp-E (37). Additionally, a recent report corroborated that Clip-170-mediated Plk1 targeting to KTs promotes K-fiber stability and chromosome alignment by recruiting Cenp-E in an MT-independent manner (38). However, the molecular mechanisms by which Plk1 recruits Cenp-E and the identity of the substrate in this process remain unknown.…”

Section: Discussionmentioning

confidence: 91%

Phosphorylation of Astrin Regulates Its Kinetochore Function

Chung

Park

Lee

et al. 2016

Journal of Biological Chemistry

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The error-free segregation of chromosomes, which requires the precisely timed search and capture of chromosomes by spindles during early mitotic and meiotic cell division, is responsible for genomic stability and is achieved by the spindle assembly checkpoint in the metaphase-anaphase transition. Mitotic kinases orchestrate M phase events, such as the reorganization of cell architecture and kinetochore (KT) composition with the exquisite phosphorylation of mitotic regulators, to ensure timely and temporal progression. However, the molecular mechanisms underlying the changes of KT composition for stable spindle attachment during mitosis are poorly understood. Here, we show that the sequential action of the kinase Cdk1 and the phosphatase Cdc14A control spindle attachment to KTs. During prophase, the mitotic spindle protein Spag5/Astrin is transported into centrosomes by Kinastrin and phosphorylated at Ser-135 and Ser-249 by Cdk1, which, in prometaphase, is loaded onto the spindle and targeted to KTs. We also demonstrate that Cdc14A dephosphorylates Astrin, and therefore the overexpression of Cdc14A sequesters Astrin in the centrosome and results in aberrant chromosome alignment. Mechanistically, Plk1 acts as an upstream kinase for Astrin phosphorylation by Cdk1 and targeting phospho-Astrin to KTs, leading to the recruitment of outer KT components, such as Cenp-E, and the stable attachment of spindles to KTs. These comprehensive findings reveal a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity.The maintenance of genome integrity during mitosis is crucial for cell survival and organismal development. To generate two daughter cells with identical genetic information, each sister chromatid must be captured by spindle microtubules (MTs), 4 aligned at the mitotic equator, and segregated toward the spindle poles. Cells build a proteinaceous structure, known as the KT, at the centromere and form a bipolar spindle with an amphitelic spindle attachment to achieve accurate chromosome segregation (1). The KT is made up of protein complexes that control its localization on the chromosome, assembly, attachment to spindle MTs, and chromosome movements, such as congression and segregation (2). KTs lacking essential proteins for KT-MT attachment, such as Knl1, Mis12, and Ndc80 protein subcomplexes, are unable to attach to spindle MTs (3), which in turn results in chromosome loss and concurrent cell death (4).Entry into mitosis is controlled by the concerted action of several mitotic kinases, such as Cyclin-dependent kinase 1 (Cdk1), Polo-like kinase 1 (Plk1), and Aurora A, whose activities are regulated indirectly in a positive feedback loop (5). Plk1 activates Cdk1 by phosphorylating and activating Cdc25, which then removes inhibitory phosphorylation at the Thr-14 and Tyr-15 sites of Cdk1. Aurora A phosphorylates Thr-210 in the active loop of Plk1 with the aid of Bora (6). Cdk1 also activates Plk1 via Bora phosphorylation to promote mit...

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“…For example, RSF1 directly binds to PLK1 to play an important role in PLK1 deposition and function at mitotic kinetochores [64]; PLK1 phosphorylates PAX3-FOXO1 to stabilize the protein and has been proposed as a rational target for treating alveolar rhabdomyosarcoma [65]; CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment [66]. Among the interactive partners with PLK1 , tumor suppressor genes are noteworthy considering the oncogenic role of PLK1 in human cancers.…”

Section: Plk1 and Human Cancermentioning

confidence: 99%

PLK1, A Potential Target for Cancer Therapy

Liu

Sun

Wang

2017

Translational Oncology

362

269

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Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1’s structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation. Finally, we discussed the key issues in the development of PLK1-targeted cancer therapy.

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CLIP-170 is required to recruit PLK1 to kinetochores during early mitosis for chromosome alignment

Cited by 31 publications

References 42 publications

CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

CLIP‐170 tethers kinetochores to microtubule plus ends against poleward force by dynein for stable kinetochore–microtubule attachment

Phosphorylation of Astrin Regulates Its Kinetochore Function

PLK1, A Potential Target for Cancer Therapy

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