Alternative titles; symbols
HGNC Approved Gene Symbol: TPX2
Cytogenetic location: 20q11.21 Genomic coordinates (GRCh38) : 20:31,739,290-31,801,800 (from NCBI)
Heidebrecht et al. (1997) determined that p100 is a nuclear proliferation-associated protein whose expression is restricted to cell cycle phases S, G2, and M. Using an mRNA differential display technique, Manda et al. (1999) isolated 2 novel cDNAs, SPON2 (605918) and C20ORF1, which they designated differentially expressed in cancerous and noncancerous lung cells-1 (DIL1) and -2 (DIL2), respectively. The full-length C20ORF1 cDNA encodes a 747-amino acid protein with a putative ATP/GTP-binding site motif. RT-PCR analysis demonstrated strong expression of C20ORF1 in lung carcinoma cell lines. Northern blot analysis detected expression in fetal lung but not in adult lung. C20ORF1 expression was also found in adult placenta, skeletal muscle, thymus, testis, and small intestine and in fetal brain, liver, and kidney,
In Xenopus egg extracts, Tpx2 is required for the Ran-GTP (601179)-dependent assembly of microtubules around chromosomes. Gruss et al. (2002) found that interfering with the function of human TPX2 in HeLa cells caused defects in microtubule organization during mitosis. Suppressing TPX2 expression by RNA interference led to the formation of 2 microtubule asters that did not interact and did not form a spindle. Gruss et al. (2002) concluded that 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.
By mass spectrometry, Kufer et al. (2002) found that TPX2 coimmunoprecipitated specifically with STK6 (AURKA; 603072) from mitotic HeLa cell extracts. Conversely, STK6 could be detected in TPX2 immunoprecipitates. Binding studies demonstrated that the N terminus of TPX2 directly interacted with the C-terminal catalytic domain of STK6. Although kinase activity was not required for their interaction, TPX2 was readily phosphorylated by STK6. Upon small interfering RNA (siRNA)-mediated elimination of TPX2 from cells, the association of STK6 with the spindle microtubules was abolished, although its association with spindle poles was unaffected. Conversely, depletion of STK6 by siRNA had no detectable influence on the localization of TPX2. Kufer et al. (2002) proposed that TPX2 is required for targeting STK6 to the spindle apparatus, and that STK6 may regulate the function of TPX2 during spindle assembly.
Joukov et al. (2006) found that the heterodimeric tumor suppressor complex BRCA1 (113705)/BARD1 (601593) was required for mitotic spindle-pole assembly and for accumulation of TPX2 on spindle poles in both HeLa cells and Xenopus egg extracts. This BRCA1/BARD1 function was centrosome independent, operated downstream of Ran GTPase, and depended upon BRCA1/BARD1 E3 ubiquitin ligase activity. Joukov et al. (2006) concluded that BRCA1/BARD1 function in mitotic spindle assembly likely contributes to its role in chromosome stability control and tumor suppression.
Bipolar spindle assembly is driven by the microtubule motor EG5 (KIF11; 148760), which can slide antiparallel microtubules apart to drive centrosome separation. Using HeLa and U2OS human osteosarcoma cells, Tanenbaum et al. (2009) found that, overexpression of KIF15 (617569) restored most spindle assembly functions in the absence of EG5 activity. KIF15 failed to separate centrosomes in prophase in EG5-inhibited U2OS cells, suggesting that KIF15 specifically functions after nuclear envelope breakdown and that KIF15 cannot replicate early phases of EG5-dependent centrosome separation. Tanenbaum et al. (2009) found that the C-terminal leucine zipper of KIF15 bound to TPX2, and that depletion of TPX2 prevented KIF15 from binding to spindles and driving bipolar spindle assembly in the absence of EG5. Tanenbaum et al. (2009) proposed that a complex of KIF15 and TPX2 can crosslink and slide 2 antiparallel microtubules apart to drive centrosome separation, but only after initial EG5-dependent centrosome separation in prophase.
By fluorescence in situ hybridization, Zhang et al. (1999) mapped the C20ORF1 gene to chromosome 20q11.2.
Gruss, O. J., Wittmann, M., Yokoyama, H., Pepperkok, R., Kufer, T., Sillje, H., Karsenti, E., Mattaj, I. W., Vernos, I. Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Nature Cell. Biol. 4: 871-879, 2002. [PubMed: 12389033] [Full Text: https://doi.org/10.1038/ncb870]
Heidebrecht, H. J., Buck, F., Steinmann, J., Sprenger, R., Wacker, H. H., Parwaresch, R. p100: a novel proliferation-associated nuclear protein specifically restricted to cell cycle phases S, G2, and M. Blood 90: 226-233, 1997. [PubMed: 9207457]
Joukov, V., Groen, A. C., Prokhorova, T., Gerson, R., White, E., Rodriguez, A., Walter, J. C., Livingston, D. M. The BRCA1/BARD1 heterodimer modulates Ran-dependent mitotic spindle assembly. Cell 127: 539-552, 2006. [PubMed: 17081976] [Full Text: https://doi.org/10.1016/j.cell.2006.08.053]
Kufer, T. A., Sillje, H. H. W., Korner, R., Gruss, O. J., Meraldi, P., Nigg, E. A. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J. Cell Biol. 158: 617-623, 2002. [PubMed: 12177045] [Full Text: https://doi.org/10.1083/jcb.200204155]
Manda, R., Kohno, T., Matsuno, Y., Takenoshita, S., Kuwano, H., Yokota, J. Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display. Genomics 61: 5-14, 1999. [PubMed: 10512675] [Full Text: https://doi.org/10.1006/geno.1999.5939]
Tanenbaum, M. E., Macurek, L., Janssen, A., Geers, E. F., Alvarez-Fernandez, M., Medema, R. H. Kif15 cooperates with Eg5 to promote bipolar spindle assembly. Curr. Biol. 19: 1703-1711, 2009. [PubMed: 19818618] [Full Text: https://doi.org/10.1016/j.cub.2009.08.027]
Zhang, Y., Heidebrecht, H.-J., Rott, A., Schlegelberger, B., Parwaresch, R. Assignment of human proliferation associated p100 gene (C20orf1) to human chromosome band 20q11.2 by in situ hybridization. Cytogenet. Cell Genet. 84: 182-183, 1999. [PubMed: 10393424] [Full Text: https://doi.org/10.1159/000015251]