Other entities represented in this entry:
HGNC Approved Gene Symbol: TACC1
Cytogenetic location: 8p11.22 Genomic coordinates (GRCh38): 8:38,728,582-38,853,028 (from NCBI)
Amplification of various chromosomal regions in human breast carcinomas has lead to the identification of protooncogenes involved in tumorigenesis. For example, MYC (190080) in 8q24, CCND1 (168461) in 11q13, and ERBB2 (164870) in 17q12 are each observed in 20% of all breast tumors. Still et al. (1999) noted that 8p11 is amplified in 10 to 15% of breast tumor samples but the only gene assigned to this region, FGFR1 (136350), is typically expressed at the same levels in normal and tumor breast tissue. By PCR analysis with primers obtained from an EST database, generation of a BAC contig spanning 380 kb of the 8p11 breast cancer amplicon-1, and probing fetal tissue libraries, Still et al. (1999) isolated a cDNA encoding TACC1. The predicted 805-amino acid TACC1 protein is rich in serine, proline, and acidic residues, has a 20-amino acid N terminus rich in tryptophan, contains 2 nuclear localization signals but no DNA- or RNA-binding domains, and has a 200-residue C terminus with extensive alpha-helical segments expected to adopt a coiled-coil structure. Northern blot analysis detected a major 8.0-kb TACC1 transcript in all tissues tested, with relatively weak expression in liver and lung.
Still et al. (1999) found that introduction of TACC1 into stable cell lines resulted in morphologic changes consistent with a transformed phenotype and in anchorage-independent growth.
By yeast 2-hybrid and coimmunoprecipitation analyses, Lauffart et al. (2002) showed that TACC1 interacted with C-terminal regions of CHTOG (CKAP5; 611142) and GAS41 (YEATS4; 602116).
During neurogenesis, the nuclei of progenitor cells of the proliferative ventricular zone oscillate in a cell cycle-dependent manner called interkinetic nuclear migration (INM). In most cell types, the nucleus closely follows the centrosome during migration; however, in neural progenitors, centrosomes remain near the ventricular zone during INM. Xie et al. (2007) showed that INM in mice was dependent on the regulation of centrosome-associated microtubules by Cep120 (613446) and Taccs. Cep120 and Taccs regulated the integrity of microtubules coupling the centrosome and the nucleus. Cep120 interacted with Taccs and regulated the localization of Tacc3 (605303) to the centrosome. Both Cep120 and Taccs were essential for maintaining the neural progenitor pool during mouse neocortical development.
Singh et al. (2012) reported that a small subset of glioblastoma multiforme tumors (GBMs; 137800) (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes FGFR1 (136350) or FGFR3 (134934) to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3 (605303), respectively. The FGFR-TACC fusion protein displayed oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrected the aneuploidy, and oral administration of an FGFR inhibitor prolonged survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. Singh et al. (2012) concluded that FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition.
Lauffart, B., Howell, S. J., Tasch, J. E., Cowell, J. K., Still, I. H. Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells. Biochem. J. 363: 195-200, 2002. [PubMed: 11903063] [Full Text: https://doi.org/10.1042/0264-6021:3630195]
Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., Liu, E. M., Reichel, J., Porrati, P., Pellegatta, S., Qiu, K., Gao, Z., and 12 others. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337: 1231-1235, 2012. [PubMed: 22837387] [Full Text: https://doi.org/10.1126/science.1220834]
Still, I. H., Hamilton, M., Vince, P., Wolfman, A., Cowell, J. K. Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene 18: 4032-4038, 1999. [PubMed: 10435627] [Full Text: https://doi.org/10.1038/sj.onc.1202801]
Xie, Z., Moy, L. Y., Sanada, K., Zhou, Y., Buchman, J. J., Tsai, L.-H. Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron 56: 79-93, 2007. [PubMed: 17920017] [Full Text: https://doi.org/10.1016/j.neuron.2007.08.026]