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Gene Review

TPX2  -  TPX2, microtubule-associated

Homo sapiens

Synonyms: C20orf1, C20orf2, DIL-2, DIL2, Differentially expressed in cancerous and non-cancerous lung cells 2, ...
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Disease relevance of TPX2

  • Abnormally expressed TPX2 has been reported in various malignancies, but less is known in lung cancer [1].
  • The present study appraised the significance of TPX2 aberrant expression for tumorigenesis and progression of human squamous cell carcinoma (SCC) in lung [1].
  • Extremely low levels of TPX2 protein were found in the normal bronchial epithelia and alveoli, whereas gradually increased TPX2 protein levels were observed in the squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor tissues [1].
  • Statistical analysis showed that the TPX2 immunohistochemistry labeling index was correlated with the differentiation grade, stage, and lymphous metastasis of SCC in lung and that TPX2 overexpression is significantly associated with decreased 5-year survival rate of the patients [1].
  • Integrated DNA-RNA analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung cancer [2].

High impact information on TPX2

  • TPX2 is required for Ran.GTP and chromatin-induced microtubule assembly in M phase extracts and mediates spontaneous microtubule assembly when present in excess over free importin alpha [3].
  • TPX2 is normally inactivated by binding to the nuclear import factor, importin alpha, and is displaced from importin alpha by the action of Ran.GTP [3].
  • The structure of the complex of Aurora A with the TPX2 activator has been reported previously [4].
  • The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation [5].
  • In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation [5].

Chemical compound and disease context of TPX2

  • The analysis of three human herpesvirus-7 (HHV-7) genes encoding phosphoprotein p100, glycoprotein B and major capsid protein respectively had previously shown the existence of distinct gene alleles, leading to the concept of HHV-7 variants [6].
  • In this study we used okadaic acid, an inhibitor of serine/threonine phosphatase 1 and 2 A, as a probe to explore the signaling pathway regulating the expression of p100 RasGAP in JEG-3 human placental choriocarcinoma cells [7].
  • CONCLUSIONS: Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long-term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki-67, PCNA, topoisomerase II-alpha, and p100 [8].

Biological context of TPX2


Anatomical context of TPX2

  • Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells [10].
  • Our results suggest that in vivo, even in the presence of duplicated centrosomes, spindle formation requires the function of TPX2 to generate a stable bipolar spindle with overlapping antiparallel microtubule arrays [10].
  • EXPERIMENTAL DESIGN AND RESULTS: The expressive status of TPX2 was firstly examined with lung cancer (L, PAa, and PG) and immortalized bronchial epithelial (C45, M-BE, Tr, and Y-BE) cell lines, and TPX2 expression was detected at both RNA and protein levels by reverse transcription-PCR and Western blotting, respectively [1].
  • CONCLUSIONS: Aberrant expression of TPX2 may play important role(s) in both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer and could serve as a prognostic predictor for the disease [1].
  • Targeting of TPX2/importin-beta complexes to poles is a key aspect in Ran-dependent control of the mitotic apparatus in mammalian cells [11].

Associations of TPX2 with chemical compounds

  • Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation [5].
  • Binding studies demonstrated that the NH2 terminus of TPX2 can directly interact with the COOH-terminal catalytic domain of Aurora-A [12].
  • Critical role of RelB serine 368 for dimerization and p100 stabilization [13].
  • We show here that, besides the C-terminal sequences, multiple functional regions, including the two alpha-helices, dimerization domain, nuclear localization sequence, and glycine-rich region, located in the N terminus of p100, also play important roles in both constitutive and inducible processing, suggesting a common mechanism for p100 processing [14].
  • Tryptic peptide analysis of the gag-related protein of MH2, p100, revealed gag-specific peptides and several unique methionine-containing peptides [15].

Physical interactions of TPX2

  • Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus [12].

Enzymatic interactions of TPX2

  • We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation [5].

Regulatory relationships of TPX2

  • Conversely, depletion of Aurora-A by siRNA had no detectable influence on the localization of TPX2 [12].
  • We conclude that APC/C(Cdh1) controls the stability of TPX2, thereby ensuring accurate regulation of the spindle assembly in the cell cycle [16].
  • Studies on routinely processed paraffin sections of specimens of malignant lymphoma, benign and malignant nevocellular tumors, and breast cancer showed that in all cases less than 40% of the Ki-67-positive growth fraction expressed p100 [17].

Other interactions of TPX2


Analytical, diagnostic and therapeutic context of TPX2


  1. Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer. Ma, Y., Lin, D., Sun, W., Xiao, T., Yuan, J., Han, N., Guo, S., Feng, X., Su, K., Mao, Y., Cheng, S., Gao, Y. Clin. Cancer Res. (2006) [Pubmed]
  2. High-resolution genomic profiles of human lung cancer. Tonon, G., Wong, K.K., Maulik, G., Brennan, C., Feng, B., Zhang, Y., Khatry, D.B., Protopopov, A., You, M.J., Aguirre, A.J., Martin, E.S., Yang, Z., Ji, H., Chin, L., Depinho, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. Gruss, O.J., Carazo-Salas, R.E., Schatz, C.A., Guarguaglini, G., Kast, J., Wilm, M., Le Bot, N., Vernos, I., Karsenti, E., Mattaj, I.W. Cell (2001) [Pubmed]
  4. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Sessa, F., Mapelli, M., Ciferri, C., Tarricone, C., Areces, L.B., Schneider, T.R., Stukenberg, P.T., Musacchio, A. Mol. Cell (2005) [Pubmed]
  5. Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Bayliss, R., Sardon, T., Vernos, I., Conti, E. Mol. Cell (2003) [Pubmed]
  6. Genetic polymorphism of human herpesvirus-7 among human populations. Franti, M., Gessain, A., Darlu, P., Gautheret-Dejean, A., Kosuge, H., Mauclère, P., Aubin, J.T., Gurtsevitch, V., Yamanishi, K., Agut, H. J. Gen. Virol. (2001) [Pubmed]
  7. A protein kinase C-independent pathway leading to c-Jun-dependent expression of 100-kDa Ras GTPase-activating protein in JEG-3 human choriocarcinoma cells. Ye, F., Bourgeade, M.F., Cayre, Y.E., Thang, M.N. Eur. J. Biochem. (2000) [Pubmed]
  8. The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma. Lehmann, J., Retz, M., Nürnberg, N., Schnöckel, U., Raffenberg, U., Krams, M., Kellner, U., Siemer, S., Weichert-Jacobsen, K., Stöckle, M. Cancer (2004) [Pubmed]
  9. Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display. Manda, R., Kohno, T., Matsuno, Y., Takenoshita, S., Kuwano, H., Yokota, J. Genomics (1999) [Pubmed]
  10. Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Gruss, O.J., Wittmann, M., Yokoyama, H., Pepperkok, R., Kufer, T., Silljé, H., Karsenti, E., Mattaj, I.W., Vernos, I. Nat. Cell Biol. (2002) [Pubmed]
  11. Importin beta is transported to spindle poles during mitosis and regulates Ran-dependent spindle assembly factors in mammalian cells. Ciciarello, M., Mangiacasale, R., Thibier, C., Guarguaglini, G., Marchetti, E., Di Fiore, B., Lavia, P. J. Cell. Sci. (2004) [Pubmed]
  12. Human TPX2 is required for targeting Aurora-A kinase to the spindle. Kufer, T.A., Silljé, H.H., Körner, R., Gruss, O.J., Meraldi, P., Nigg, E.A. J. Cell Biol. (2002) [Pubmed]
  13. Critical role of RelB serine 368 for dimerization and p100 stabilization. Maier, H.J., Marienfeld, R., Wirth, T., Baumann, B. J. Biol. Chem. (2003) [Pubmed]
  14. Regulation of NF-kappa B2 p100 processing by its cis-acting domain. Qing, G., Qu, Z., Xiao, G. J. Biol. Chem. (2005) [Pubmed]
  15. Avian oncovirus MH2: molecular cloning of proviral DNA and structural analysis of viral RNA and protein. Jansen, H.W., Patschinsky, T., Bister, K. J. Virol. (1983) [Pubmed]
  16. Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit. Stewart, S., Fang, G. Mol. Cell. Biol. (2005) [Pubmed]
  17. p100: a novel proliferation-associated nuclear protein specifically restricted to cell cycle phases S, G2, and M. Heidebrecht, H.J., Buck, F., Steinmann, J., Sprenger, R., Wacker, H.H., Parwaresch, R. Blood (1997) [Pubmed]
  18. TPX2, A novel xenopus MAP involved in spindle pole organization. Wittmann, T., Wilm, M., Karsenti, E., Vernos, I. J. Cell Biol. (2000) [Pubmed]
  19. Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity. Maxwell, C.A., Keats, J.J., Belch, A.R., Pilarski, L.M., Reiman, T. Cancer Res. (2005) [Pubmed]
  20. 20q11.1 amplification in giant-cell tumor of bone: Array CGH, FISH, and association with outcome. Smith, L.T., Mayerson, J., Nowak, N.J., Suster, D., Mohammed, N., Long, S., Auer, H., Jones, S., McKeegan, C., Young, G., Bos, G., Plass, C., Morrison, C. Genes Chromosomes Cancer (2006) [Pubmed]
  21. Assignment of human proliferation associated p100 gene (C20orf1) to human chromosome band 20q11.2 by in situ hybridization. Zhang, Y., Heidebrecht, H., Rott, A., Schlegelberger, B., Parwaresch, R. Cytogenet. Cell Genet. (1999) [Pubmed]
  22. Expression and function of a variant T cell receptor complex lacking CD3-gamma. Pérez-Aciego, P., Alarcón, B., Arnaiz-Villena, A., Terhorst, C., Timón, M., Segurado, O.G., Regueiro, J.R. J. Exp. Med. (1991) [Pubmed]
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