Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint

Wei, Randy; Ngo, Bryan; Wu, Guikai; Lee, Wen‐Hwa

doi:10.1091/mbc.e11-01-0012

Cited by 64 publications

(71 citation statements)

References 58 publications

(76 reference statements)

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“…Deletion and overexpression of S. pombe Fin1 results in spindle formation defects, and fin1 genetically interacts with the spindle checkpoint proteins Mad2 and Bub1 (Grallert and Hagan, 2002). In humans, Nek2 also regulates chromosome alignment and signaling of the spindle assembly checkpoint by phosphorylating the kinetochore protein Ndc80/Hec1 (Wei et al, 2011). Our observations using MORN1 as a marker for the spindle indicate that in mutant V-A15 the spindle pole divides and the structure we observe in Fig.…”

Section: Discussionsupporting

confidence: 53%

The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant

Chen

Gubbels

2013

Journal of Cell Science

101

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SummaryThe pathology and severity of toxoplasmosis results from the rapid replication cycle of the apicomplexan parasite Toxoplasma gondii. The tachyzoites divide asexually through endodyogeny, wherein two daughter cells bud inside the mother cell. Before mitosis is completed, the daughter buds form around the duplicated centrosomes and subsequently elongate to serve as the scaffold for organellogenesis and organelle partitioning. The molecular control mechanism of this process is poorly understood. Here, we characterized a T. gondii NIMA-related kinase (Nek) ortholog that was identified in a chemical mutagenesis screen. A temperaturesensitive mutant, V-A15, possesses a Cys316Arg mutation in TgNek1 (a novel mutant allele in Neks), which is responsible for growth defects at the restrictive temperature. Phenotypic analysis of V-A15 indicated that TgNek1 is essential for centrosome splitting, proper formation of daughter cells and faithful segregation of genetic material. In vitro kinase assays showed that the mutation abolishes the kinase activity of TgNek1. TgNek1 is recruited to the centrosome prior to its duplication and localizes on the duplicated centrosomes facing the spindle poles in a cell-cycle-dependent manner. Mutational analysis of the activation loop suggests that localization and activity are spatio-temporally regulated by differential phosphorylation. Collectively, our results identified a novel temperature-sensitive allele for a Nek kinase and highlight its essential function in centrosome splitting in Toxoplasma. Moreover, these results conclusively show for the first time that Toxoplasma bud assembly is facilitated by the centrosome because defective centrosome splitting results in single daughter cell budding.

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Section: Discussionsupporting

confidence: 53%

The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant

Chen

Gubbels

2013

Journal of Cell Science

101

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“…In addition, serine 165 within the NDC80 CH domain is a target for the kinase NEK2, and this phosphorylation is important for chromosome alignment and the SAC (Wei et al, 2011). Cells expressing a non-phosphorylatable mutation of NDC80 at serine 165 are unable to recruit MAD1-MAD2 to kinetochores and exhibit premature anaphase onset with erroneous chromosome segregation.…”

Section: Knl1mentioning

confidence: 99%

The KMN protein network – chief conductors of the kinetochore orchestra

Varma

Salmon

2012

Journal of Cell Science

115

108

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SummarySuccessful completion of mitosis requires that sister kinetochores become attached end-on to the plus ends of spindle microtubules (MTs) in prometaphase, thereby forming kinetochore microtubules (kMTs) that tether one sister to one spindle pole and the other sister to the opposite pole. Sites for kMT attachment provide at least four key functions: robust and dynamic kMT anchorage; force generation that can be coupled to kMT plus-end dynamics; correction of errors in kMT attachment; and control of the spindle assembly checkpoint (SAC). The SAC typically delays anaphase until chromosomes achieve metaphase alignment with each sister kinetochore acquiring a full complement of kMTs. Although it has been known for over 30 years that MT motor proteins reside at kinetochores, a highly conserved network of protein complexes, called the KMN network, has emerged in recent years as the primary interface between the kinetochore and kMTs. This Commentary will summarize recent advances in our understanding of the role of the KMN network for the key kinetochore functions, with a focus on human cells.

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“…NDC80 expression in all cells undergoing division is high, and it is not expressed in terminally differentiated cells. This protein maintains chromosome stability (Wei et al, 2011;Wei et al, 2014), and in cells with abnormal NDC80 expression, spindle checkpoint dysfunction, abnormal chromosome separation, and cell cycle disorder may occur, perhaps ultimately leading to tumor formation (Alushin et al, 2012;Tang and Toda, 2015). NDC80 assembly plays an important role in the spindle checkpoint process.…”

Section: Discussionmentioning

confidence: 99%

NDC80 promotes proliferation and metastasis of colon cancer cells

Xing¹,

Wu²,

Chen³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Chromosome instability is a common feature of tumor cells, and may be an important mechanism in tumor formation. Nuclear division cycle 80 (NDC80) is closely associated with the stability of chromosomes. Therefore, we investigated the relationship between NDC80 and development of colon cancer using a range of methods. Western blotting and immunohistochemistry were employed to determine the expression of this protein in different colon cells and tissues, cell proliferation was measured with an MTT assay, levels of proliferating cell nuclear antigen were examined by immunofluorescence, and cell migration was observed using wound healing tests. Our results showed that the expression of NDC80 in colon cancer cells (CACO2, HCT8, HCT116, and SW480) and tissues (from 20 patients) was higher than that in controls. Moreover, cell proliferation and migration rates were elevated in cells transfected with NDC80 compared to control groups. In summary, NDC80 promotes the proliferation and metastasis of colon cancer cells, and may constitute a new target for gene therapy in treating

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Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint

Cited by 64 publications

References 58 publications

The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant

The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant

The KMN protein network – chief conductors of the kinetochore orchestra

NDC80 promotes proliferation and metastasis of colon cancer cells

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