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Gene Review

NDC80  -  NDC80 kinetochore complex component

Homo sapiens

Synonyms: HEC, HEC1, Highly expressed in cancer protein, HsHec1, KNTC2, ...
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Disease relevance of NDC80


High impact information on NDC80

  • We report here that Ndc80/Hec1 functions in regulating kinetochore microtubule plus-end dynamics and attachment stability [6].
  • The N terminus of Hec1 is phosphorylated by Aurora B kinase in vitro, and cells expressing N-terminal nonphosphorylatable mutants of Hec1 exhibit an increase in merotelic attachments, hyperstretching of centromeres, and errors in chromosome segregation [6].
  • One of the gene products, Ndc80p, shows homology to human HEC protein (Chen, Y., D.J. Riley, P-L. Chen, and W-H. Lee. 1997. Mol. Cell Biol. 17:6049-6056) and temperature-sensitive mutants show defects in chromosome segregation [7].
  • Addition of sodium molybdate, ATP, and GTP to homogenates of endometrial tissue or HEC-1 cells produces increases in EB levels similar to those obtained by the addition of cGMP [1].
  • The products of this HEC-1 oligoisoadenylate synthetase consist mainly of dimers, trimers, and tetramers as found in other cell lines after interferon treatment [8].

Chemical compound and disease context of NDC80


Biological context of NDC80

  • Architecture of the human ndc80-hec1 complex, a critical constituent of the outer kinetochore [14].
  • These results suggest that the HEC protein may play an important role in chromosome segregation during M phase [15].
  • HEC protein is expressed most abundantly in the S and M phases of rapidly dividing cells but not in terminal differentiated cells [15].
  • HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis [15].
  • Inactivation of HEC by microinjection of specific monoclonal antibodies into cells during interphase severely disturbs the subsequent mitoses [15].

Anatomical context of NDC80

  • Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites [16].
  • Here, we show that depletion of either Nuf2 or Hec1 by RNAi in HeLa cells results in reduction of both proteins at kinetochores and in the cytoplasm [17].
  • The ERbetacx transcript is expressed in testis, ovary, thymus and prostate as well as in human cultured cell lines such as HEC-1, HOS-TE85 and Saos-2 cells [18].
  • Moreover, a polyclonal antibody, anti HEC1, specifically immunoprecipitated the BRL 3A BP from the same conditioned media, as well as from rat cerebrospinal and amniotic fluid and from conditioned medium of cells isolated from the neurointermediate lobe of adult rat pituitary [19].
  • However, HEC-1 cells were susceptible to the cytotoxicity of natural killer (NK) cells, and interferon enhanced such NK activity [3].

Associations of NDC80 with chemical compounds

  • The protein encoded by the human gene HEC (highly expressed in cancer) contains 642 amino acids and a long series of leucine heptad repeats at its C-terminal region [15].
  • Here we show that human Hec1 is a serine phosphoprotein and that it binds specifically to the mitotic regulatory kinase Nek2 during G(2)/M [20].
  • Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells [21].
  • Epidermal growth factor-stimulated proliferation of HEC-1 cells was inhibited by RC-160 in a dose-dependent manner [10].
  • The growth of HEC cells was unaffected by either progesterone or medroxyprogesterone acetate, a slowly metabolized progestin, at about 10(-6) M levels but was inhibited by about 10(-5) M concentrations of these compounds [11].

Regulatory relationships of NDC80


Other interactions of NDC80


Analytical, diagnostic and therapeutic context of NDC80


  1. Rapid changes in specific estrogen binding elicited by cGMP or cAMP in cytosol from human endometrial cells. Fleming, H., Blumenthal, R., Gurpide, E. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  2. Compartmentalization of the IgG immune response to HIV-1 in breast milk. Becquart, P., Hocini, H., Garin, B., Sépou, A., Kazatchkine, M.D., Bélec, L. AIDS (1999) [Pubmed]
  3. Resistance to interferon of a human adenocarcinoma cell line, HEC-1, and its sensitivity to natural killer cell action. Chen, H.Y., Sato, T., Fuse, A., Kuwata, T., Content, J. J. Gen. Virol. (1981) [Pubmed]
  4. Cross-sensitivity between interferon and uv in human cell strains: IFr, HEC-1, and CRL1200. Suzuki, N., Kojima, T., Kuwata, T., Nishimaki, J., Takakubo, Y., Miki, T. Virology (1984) [Pubmed]
  5. Characteristics of cyclic nucleotide dependent regulation of cytoplasmic E2 binders in cultured endometrial and breast cells. Fleming, H., Blumenthal, R., Gurpide, E. J. Steroid Biochem. (1984) [Pubmed]
  6. Kinetochore microtubule dynamics and attachment stability are regulated by hec1. Deluca, J.G., Gall, W.E., Ciferri, C., Cimini, D., Musacchio, A., Salmon, E.D. Cell (2006) [Pubmed]
  7. Analysis of the Saccharomyces spindle pole by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Wigge, P.A., Jensen, O.N., Holmes, S., Souès, S., Mann, M., Kilmartin, J.V. J. Cell Biol. (1998) [Pubmed]
  8. Abnormal behavior of interferon-induced enzymatic activities in an interferon-resistant cell line. Verhaegen, M., Divizia, M., Vandenbussche, P., Kuwata, T., Content, J. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  9. Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcription activation. McInerney, E.M., Katzenellenbogen, B.S. J. Biol. Chem. (1996) [Pubmed]
  10. Inhibition of human endometrial cancer cell growth in vitro and in vivo by somatostatin analog RC-160. Mishima, M., Yano, T., Jimbo, H., Yano, N., Morita, Y., Yoshikawa, H., Schally, A.V., Taketani, Y. Am. J. Obstet. Gynecol. (1999) [Pubmed]
  11. Metabolism and effects of progesterone in the human endometrial adenocarcinoma cell line HEC-1. Satyaswaroop, P.G., Frost, A., Gurpide, E. Steroids (1980) [Pubmed]
  12. Transferrin increases adherence of iron-deprived Neisseria gonorrhoeae to human endometrial cells. Heine, R.P., Elkins, C., Wyrick, P.B., Sparling, P.F. Am. J. Obstet. Gynecol. (1996) [Pubmed]
  13. In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate. Grenman, S.E., Roberts, J.A., England, B.G., Grönroos, M., Carey, T.E. Gynecol. Oncol. (1988) [Pubmed]
  14. Architecture of the human ndc80-hec1 complex, a critical constituent of the outer kinetochore. Ciferri, C., De Luca, J., Monzani, S., Ferrari, K.J., Ristic, D., Wyman, C., Stark, H., Kilmartin, J., Salmon, E.D., Musacchio, A. J. Biol. Chem. (2005) [Pubmed]
  15. HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis. Chen, Y., Riley, D.J., Chen, P.L., Lee, W.H. Mol. Cell. Biol. (1997) [Pubmed]
  16. Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites. DeLuca, J.G., Dong, Y., Hergert, P., Strauss, J., Hickey, J.M., Salmon, E.D., McEwen, B.F. Mol. Biol. Cell (2005) [Pubmed]
  17. Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. DeLuca, J.G., Howell, B.J., Canman, J.C., Hickey, J.M., Fang, G., Salmon, E.D. Curr. Biol. (2003) [Pubmed]
  18. Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human. Ogawa, S., Inoue, S., Watanabe, T., Orimo, A., Hosoi, T., Ouchi, Y., Muramatsu, M. Nucleic Acids Res. (1998) [Pubmed]
  19. Expression of the BRL-3A insulin-like growth factor binding protein (rBP-30) in the rat central nervous system. Lamson, G., Pham, H., Oh, Y., Ocrant, I., Schwander, J., Rosenfeld, R.G. Endocrinology (1989) [Pubmed]
  20. Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation. Chen, Y., Riley, D.J., Zheng, L., Chen, P.L., Lee, W.H. J. Biol. Chem. (2002) [Pubmed]
  21. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Charnock-Jones, D.S., Sharkey, A.M., Rajput-Williams, J., Burch, D., Schofield, J.P., Fountain, S.A., Boocock, C.A., Smith, S.K. Biol. Reprod. (1993) [Pubmed]
  22. HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins. Chen, Y., Sharp, Z.D., Lee, W.H. J. Biol. Chem. (1997) [Pubmed]
  23. Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Martin-Lluesma, S., Stucke, V.M., Nigg, E.A. Science (2002) [Pubmed]
  24. The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Joseph, J., Liu, S.T., Jablonski, S.A., Yen, T.J., Dasso, M. Curr. Biol. (2004) [Pubmed]
  25. Identification of two novel components of the human NDC80 kinetochore complex. Bharadwaj, R., Qi, W., Yu, H. J. Biol. Chem. (2004) [Pubmed]
  26. Effects of hepatocyte growth factor on the expression of matrix metalloproteinases and their tissue inhibitors during the endometrial cancer invasion in a three-dimensional coculture. Park, Y.H., Ryu, H.S., Choi, D.S., Chang, K.H., Park, D.W., Min, C.K. Int. J. Gynecol. Cancer (2003) [Pubmed]
  27. Expression of interleukin-8 in human metastatic endometrial carcinoma cells and its regulation by inflammatory cytokines. Berry, K.K., Varney, M.L., Dave, B.J., Bucana, C.D., Fidler, I.J., Singh, R.K. Int. J. Gynecol. Cancer (2001) [Pubmed]
  28. In vitro inhibition of endometrial cancer growth by a neonatal rat testicular secretory product. Rosenwaks, Z., Liu, H.C., Jones, H.W., Tseng, L., Stone, M.L. J. Clin. Endocrinol. Metab. (1981) [Pubmed]
  29. Characterization of urinary insulin-like growth factor binding proteins. Hasegawa, Y., Cohen, P., Yorgin, P., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  30. A polarized human endometrial cell line that binds and transports polymeric IgA. Ball, J.M., Moldoveanu, Z., Melsen, L.R., Kozlowski, P.A., Jackson, S., Mulligan, M.J., Mestecky, J.F., Compans, R.W. In Vitro Cell. Dev. Biol. Anim. (1995) [Pubmed]
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