NDC80

Official Full Name

NDC80 kinetochore complex component

Organism

Homo sapiens

GeneID

10403

Background

This gene encodes a component of the NDC80 kinetochore complex. The encoded protein consists of an N-terminal microtubule binding domain and a C-terminal coiled-coiled domain that interacts with other components of the complex. This protein functions to organize and stabilize microtubule-kinetochore interactions and is required for proper chromosome segregation. [provided by RefSeq, Oct 2011]

Synonyms

HEC; HEC1; TID3; KNTC2; HsHec1; hsNDC80;

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Detailed Information

The nuclear division cycle 80 (Ndc80) complex is a heterotetrameric protein complex that plays an important role in cell mitosis. Abnormal expression of the Ndc80 complex causes chromosomal abnormalities, leading to genomic instability, which is a major factor in all tumorigenesis.

Structure and Function of the Ndc80 Complex

The Ndc80 complex is a heterotetrameric protein complex composed of Ndc80 (nuclear division cycle 80), Nuf2 (ndc80 kinetochore complex component), Spc24 (spindle pole body component 24 homolog) and Spc25 (spindle pole body component 25 homolog). It is 57 nm long and has a dumbbell shape. Ndc80 and Nuf2, Spc24 and Spc25 form two heterodimeric spherical domains, respectively, which are separated by a rod-like structure formed by coiled coils and connected by a tetramerization domain. The circular secondary structure in the coiled-coil domain forms a kink, which allows the molecule to bend and form a protein-protein action platform that facilitates interaction with the microtubule.

The Ndc80 complex can be bundled into a microtubule mesh to create an arrow-like appearance that helps bridge the kinetochore with the microtube. During cell division, the microtubule-based spindle is ligated with paired sister chromatids, captured and arranged in the middle of the cell. The kinetochore assembled on the sister chromatid interacts with the spindle microtubule to form a kinetochore-microtubule attachment. Kinesthetic - Microtubules must be strong enough to take advantage of the forces generated by microtubule dynamics to ensure chromosome motility and thus move toward the cell poles. The Ndc80 complex plays an important role in the formation and maintenance of robust kinetochore-particle attachments and is essential in the spindle checkpoint signaling pathway. Abnormal expression of Ndc80 complex causes microtubule-associated protein imbalance, microtubule dynamics disruption, and mitotic chromosome segregation abnormalities, leading to the formation of aneuploid cells, which is one of the characteristics of tumorigenesis. Therefore, there is a close relationship between the components of the Ndc80 complex and the tumor.

Figure 1. Model of the Ndc80 complex bridging two Dam1 complex rings, separated by 33 nm. (Kim, J. O., et al. 2017)

Ndc80 Complex and Tumor

A liver cancer-related study showed that the expression of Ndc80 mRNA in tumor tissues of 47 patients with liver cancer was higher than that in adjacent normal tissues. Ndc80 gene silencing by lentiviral transfection with Ndc80-siRNA inhibited the proliferation of SMMC-7721 hepatoma cell line cultured in vitro. The induction of apoptosis was initiated, demonstrating that Ndc80 induces hepatocarcinogenesis mainly through its pro-augmentation and anti-apoptotic effects. In osteosarcoma, 84.6% of tumor tissues expressed Ndc80 mRNA higher than adjacent normal tissues. Its expression level is related to tumor TNM stage, distant metastasis, etc., and Ndc80 is an independent prognostic indicator.

Xing et al. found that the expression of Ndc80 protein in colon cancer cell lines such as CACO2, HCT8, HCT116 and SW480 was higher than that in normal intestinal epithelial NCM460 cell line. After transfection of the Ndc80 gene, cell proliferation was significantly accelerated and showed a stronger metastatic potential. Compared with 76 mitotic spindle checkpoint genes in 10 breast cancer tissues and 5 normal breast tissues, Ndc80 expression was significantly up-regulated in breast cancer tissues with high invasive grade, 10 times higher than normal breast tissue, and 71. 4 % of benign breast tumors also have high expression of Ndc80, but only 3 times higher than normal breast tissue, which proves that Ndc80 is an effective indicator for judging the malignant transformation of breast lesions.

References:

Xing, X. K. , Wu, H. Y. , Chen, H. L. , & Feng, H. G. . (2016). Ndc80 promotes proliferation and metastasis of colon cancer cells. Genetics and Molecular Research, 15(2).
Kim, J. O. , Zelter, A. , Umbreit, N. T. , Bollozos, A. , Riffle, M. , & Johnson, R. , et al. (2017). The ndc80 complex bridges two dam1 complex rings. Elife,.
Zhu, P. , Jin, J. , Liao, Y. , Li, J. , & He, S. . (2015). A novel prognostic biomarker spc24 up-regulated in hepatocellular carcinoma. Oncotarget, 6(38), 41383-4139.

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