Protein Complex NDC80: Properties, Functions, and Possible Role in Pathophysiology of Cell Division

Ustinov, N B; Korshunova, A. V.; Gudimchuk, Nikita

doi:10.1134/s0006297920040057

Cited by 15 publications

(20 citation statements)

References 105 publications

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“…In KT-MT attachment, spindle MTs attach end-on to KTs, a number of conserved protein complexes on chromosomes. The Ndc80 complex is one of the core kinetochore components that plays a primary role in the attachment of MTs to chromosomes ( Cheeseman and Desai, 2008 ; Ustinov et al, 2020 ). Astrin, which forms a complex with small kinetochore associated protein (SKAP) and other partners that include MYC binding protein (MYCBP) and dynein light chain (LC8), also play key roles in stabilizing KT-MT attachment ( Schmidt et al, 2010 ; Dunsch et al, 2011 ; Kern et al, 2017 ).…”

Section: The Dynamic Localization Of Astrin In Mitosismentioning

confidence: 99%

Astrin: A Key Player in Mitosis and Cancer

Ying

Yang

et al. 2020

Front. Cell Dev. Biol.

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Astrin, which is a spindle-associated protein, was found to be closely related to mitotic spindle formation and maintenance. It interacts with other spindle-related proteins to play a key role in maintaining the attachment of the kinetochore-microtubule and integrity of centrosomes and promoting the centriole duplication. In addition, Astrin was quite recently found to be abnormally highly expressed in a variety of cancers. Astrin promotes the development of cancer by participating in various molecular pathways and is considered as a potential prognostic and survival predictor.

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Section: The Dynamic Localization Of Astrin In Mitosismentioning

confidence: 99%

Astrin: A Key Player in Mitosis and Cancer

Ying

Yang

et al. 2020

Front. Cell Dev. Biol.

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“…However, the mechanism underlying its role in the prognosis of EC is yet to be investigated. NDC80, which is a component of the essential kinetochoreassociated NDC80 complex and is required for chromosome segregation and spindle checkpoint activity, was observed to inhibit cancer cell proliferation and induce apoptosis after knockdown (Qu et al, 2014;Liu et al, 2019;Ustinov et al, 2020). Xing et al (2016) found that NDC80 promotes the proliferation and metastasis of colon cancer cells by promoting aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Four-Gene Signature With Prognostic Significance in Endometrial Cancer Using Weighted-Gene Correlation Network Analysis

2021

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Endometrial hyperplasia (EH) is a precursor for endometrial cancer (EC). However, biomarkers for the progression from EH to EC and standard prognostic biomarkers for EC have not been identified. In this study, we aimed to identify key genes with prognostic significance for the progression from EH to EC. Weighted-gene correlation network analysis (WGCNA) was used to identify hub genes utilizing microarray data (GSE106191) downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified from the Uterine Corpus Endometrial Carcinoma (UCEC) dataset of The Cancer Genome Atlas database. The Limma-Voom R package was applied to detect differentially expressed genes (DEGs; mRNAs) between cancer and normal samples. Genes with |log2 (fold change [FC])| > 1.0 and p < 0.05 were considered as DEGs. Univariate and multivariate Cox regression and survival analyses were performed to identify potential prognostic genes using hub genes overlapping in the two datasets. All analyses were conducted using R Bioconductor and related packages. Through WGCNA and overlapping genes in hub modules with DEGs in the UCEC dataset, we identified 42 hub genes. The results of the univariate and multivariate Cox regression analyses revealed that four hub genes, BUB1B, NDC80, TPX2, and TTK, were independently associated with the prognosis of EC (Hazard ratio [95% confidence interval]: 0.591 [0.382–0.912], p = 0.017; 0.605 [0.371–0.986], p = 0.044; 1.678 [1.132–2.488], p = 0.01; 2.428 [1.372–4.29], p = 0.02, respectively). A nomogram was established with a risk score calculated using the four genes’ coefficients in the multivariate analysis, and tumor grade and stage had a favorable predictive value for the prognosis of EC. The survival analysis showed that the high-risk group had an unfavorable prognosis compared with the low-risk group (p < 0.0001). The receiver operating characteristic curves also indicated that the risk model had a potential predictive value of prognosis with area under the curve 0.807 at 2 years, 0.783 at 3 years, and 0.786 at 5 years. We established a four-gene signature with prognostic significance in EC using WGCNA and established a nomogram to predict the prognosis of EC.

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“…Within the centromere-proximal region, which is more than 20 nm away from the outer kinetochore and the reference protein Spc105, Cse4 and CBF3 colocalize (measured with its constituent Cep3) with each other as well as with the C-termini of both outer kinetochore receptors Mif2 and Cnn1. Hamilton et al, 2019;Jenni et al, 2017;Ustinov et al, 2020). Zhang et al, 2018).…”

Section: Kinetochore Subunits Are Organized Functionally Along the Spindle Axismentioning

confidence: 99%

Nanoscale structural organization and stoichiometry of the budding yeast kinetochore

Cieslinski¹,

Wu²,

Neechyporenko³

et al. 2021

Preprint

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Proper chromosome segregation is crucial for cell division. In eukaryotes, this is achieved by the kinetochore, an evolutionarily conserved multi-protein complex that physically links the DNA to spindle microtubules, and takes an active role in monitoring and correcting erroneous spindle-chromosome attachments. Our mechanistic understanding of these functions, and how they ensure an error-free outcome of mitosis, is still limited, partly because we lack a comprehensive understanding of the kinetochore structure in the cell. In this study, we use single molecule localization microscopy to visualize individual kinetochore complexes in situ in budding yeast. For all major kinetochore proteins, we measured abundance and position within the metaphase kinetochore. Based on this comprehensive dataset, we propose a quantitative model of the budding yeast kinetochore. While confirming many aspects of previous reports based on bulk imaging of kinetochores, our results present a somewhat different but unifying model of the inner kinetochore. We find that the centromere-specialized histone Cse4 is present in more than two copies per kinetochore along with its binding partner Mif2.

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Protein Complex NDC80: Properties, Functions, and Possible Role in Pathophysiology of Cell Division

Cited by 15 publications

References 105 publications

Astrin: A Key Player in Mitosis and Cancer

Astrin: A Key Player in Mitosis and Cancer

Identification of a Four-Gene Signature With Prognostic Significance in Endometrial Cancer Using Weighted-Gene Correlation Network Analysis

Nanoscale structural organization and stoichiometry of the budding yeast kinetochore

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