The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly

Hata, Shoji; Peidro, Ana Pastor; Panic, Marko; Liu, Peng; Atorino, Enrico; Funaya, Charlotta; Jäkle, Ursula; Pereira, Gislene; Schiebel, Elmar

doi:10.1038/s41556-019-0382-6

Cited by 52 publications

(57 citation statements)

References 67 publications

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“…Overexpression of Kif15 could drive bipolar spindle formation in the absence of Eg5 activity (Tanenbaum et al , ; Vanneste et al , ). Furthermore, it is suggested that the machinery of centrosome separation at the onset of mitosis is coordinated by redundant mechanisms (Hata et al , ). The results of our study suggest that human cells possess the redundant mechanism of canonical centrosomal and NuMA‐mediated acentrosomal pathways to promote spindle bipolarity.…”

Section: Discussionmentioning

confidence: 99%

“…At the onset of centrosome separation, the evolutionary conserved kinesin Eg5 (Enos & Morris, 1990;Hagan & Yanagida, 1990;Heck et al, 1993;Blangy et al, 1995) is loaded onto centrosomes. Therefore, the centrosomal microtubules promote the initial steps establishing mitotic spindle bipolarity (Megraw et al, 2001;Bertran et al, 2011;Smith et al, 2011;Kaseda et al, 2012;Hata et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Nu MA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

et al. 2019

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In most animal cells, mitotic spindle formation is mediated by coordination of centrosomal and acentrosomal pathways. At the onset of mitosis, centrosomes promote spindle bipolarization. However, the mechanism through which the acentrosomal pathways facilitate the establishment of spindle bipolarity in early mitosis is not completely understood. In this study, we show the critical roles of nuclear mitotic apparatus protein (NuMA) in the generation of spindle bipolarity in acentrosomal human cells. In acentrosomal human cells, we found that small microtubule asters containing NuMA formed at the time of nuclear envelope breakdown. In addition, these asters were assembled by dynein and the clustering activity of NuMA. Subsequently, NuMA organized the radial array of microtubules, which incorporates Eg5, and thus facilitated spindle bipolarization. Importantly, in cells with centrosomes, we also found that NuMA promoted the initial step of spindle bipolarization in early mitosis. Overall, these data suggest that canonical centrosomal and NuMA-mediated acentrosomal pathways redundantly promote spindle bipolarity in human cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nu MA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

et al. 2019

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“…Human cells undergo centrosome separation through two temporally distinct pathways, the prophase pathway and the prometaphase pathway [96][97][98]. By contrast, yeasts have adopted only the prometaphase pathway.…”

Section: Force Generation In Human Prophase Cellsmentioning

confidence: 99%

“…By contrast, yeasts have adopted only the prometaphase pathway. Recent analysis has uncovered key players acting in the prophase pathway and their individual roles [97]. Duplicated centrosomes in human cells remain closely linked during interphase, in a process called centrosome cohesion.…”

Section: Force Generation In Human Prophase Cellsmentioning

confidence: 99%

“…KIFC3 forms homotetramers and interconnects a special centrosome-associated microtubule network, thereby producing pulling forces towards the centrosomes. Upon mitotic entry, KIFC3 is inactivated by the NEK2 protein kinase, which also promotes the dissolution of the linker [97]. Antagonising outward forces are produced by Kineisn-5/KIF11 in both prophase and prometaphase pathways.…”

Section: Force Generation In Human Prophase Cellsmentioning

confidence: 99%

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How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

Yukawa¹,

Teratani²,

Toda³

2020

Preprint

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The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

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KIF11 serves as a cell cycle mediator in childhood acute lymphoblastic leukemia

Zhu,

Chen,

Kang

et al. 2023

J Cancer Res Clin Oncol

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Objective To identify key gene in childhood acute lymphoblastic leukemia (ALL) through weighted gene co-expression network analysis (WGCNA), and their enriched biological functions and signaling pathways. Methods Array data of the GSE73578 dataset, involving 46 childhood ALL samples, were acquired from the Gene Expression Omnibus (GEO) database. Hub modules associated with childhood ALL were screened out by WGCNA. Enriched biological functions and signaling pathways were then identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by overlapping those between down-regulated genes in GSE73578, GSE4698 and the hub module. Guilt by association (GBA) was adopted to verify the function of the identified KIF11 gene and to predict its target genes. Regulatory effects of KIF11 on the proliferation and cell cycle progression of ALL in vitro were determined by cytological experiments. Results WGCNA showed that the yellow module was the most relevant to childhood ALL treatment, containing 698 genes that were enriched in cell division, mitotic nuclear division, DNA replication and DNA repair, cell cycle, DNA replication and the P53 signaling pathway. The KIF11 gene was screened out and predicted as a cell cycle mediator in childhood ALL. Knockdown of KIF11 in ALL cells inhibited cell proliferation and arrested cell cycle progression in G2/M phase. Conclusions The KIF11 gene is critical in the treatment process of childhood ALL, which is a promising therapeutic target for childhood ALL.

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The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly

Cited by 52 publications

References 67 publications

Nu MA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

Nu MA assemblies organize microtubule asters to establish spindle bipolarity in acentrosomal human cells

How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

KIF11 serves as a cell cycle mediator in childhood acute lymphoblastic leukemia

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