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Gene Review

TBX2  -  T-box 2

Homo sapiens

Synonyms: T-box protein 2, T-box transcription factor TBX2
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Disease relevance of TBX2


High impact information on TBX2

  • Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers [4].
  • We found TBX2 to be amplified in a subset of primary human breast cancers, indicating that it might contribute to breast cancer development [4].
  • Functional dissection of the ET protein reveals a novel transcription-repression domain highly conserved among ET, human TBX3, and TBX2 [5].
  • We also report that both the MSEu and MSEi are recognized by the brachyury-related transcription factor Tbx2, a member of the recently described T-box family, and that Tbx2 is expressed in melanocyte and melanoblast cell lines but not in melanoblast precursor cells [6].
  • In the Hesr1-misexpressing heart, the boundaries of the AV canal are poorly defined, and the expression levels of specific markers of the AV myocardium, Bmp2 and Tbx2, are either very weak or undetectable [7].

Biological context of TBX2


Anatomical context of TBX2

  • TBX2 expression and its induction by retinoic acid was also observed in normal human and nonmalignant mouse melanocytes [3].
  • Northern blot analysis identified two major TBX2 expression fetal kidney and lung; and in adult kidney, lung, ovary, prostate, spleen, and testis [11].
  • Here, we show that genetic deletion of SAFB1 in mouse embryonic fibroblasts (MEF) leads to spontaneous immortalization and altered expression of two proteins involved in immortalization and escape from senescence: low levels of p19(ARF) and high levels of TBX2 [12].
  • Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2 [13].
  • Ectopic expression of Tbx3, a transcriptional repressor that belongs to the Tbx2/3/4/5 subfamily of T-box transcriptional regulators, in the forelimb results in a rostral shift in the position of the limb along the main body axis [14].

Associations of TBX2 with chemical compounds


Regulatory relationships of TBX2

  • Tbx2 is a transcriptional repressor implicated in several developmental processes and which has also been implicated in cancer through its ability to suppress senescence via repression of the p19(ARF) and p21(Cip1) (CDKN1A) promoters [16].

Other interactions of TBX2

  • Whereas the core nucleotides required for interaction of the archetypal T-box protein Brachyury with a consensus T-site are conserved in the variant site, additional flanking nucleotides contribute to the specificity of TBX2 binding [17].
  • Coduplication of MYC and TBX2 was common in the in situ and invasive lesions from the deleterious mutation carriers [18].
  • TBX4, a human member of the Tbx2/3/4/5 subfamily, has been identified and characterized from a high-throughput genomic sequence [19].
  • Support for this hypothesis comes from studies demonstrating that many of the amplified genes are over-expressed in breast cancer cell lines and tumors, and that the RPS6KB1, TBX2, and PPM1D genes from the region, that are amplified and over-expressed in breast tumors and cell lines, contribute to tumor formation and/or tumor progression [20].
  • S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RADS1C amplification was seen in only 3% of tumors [21].


  1. Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Vance, K.W., Carreira, S., Brosch, G., Goding, C.R. Cancer Res. (2005) [Pubmed]
  2. Expression of Drosophila omb-related T-box genes in the developing human and mouse neural retina. Sowden, J.C., Holt, J.K., Meins, M., Smith, H.K., Bhattacharya, S.S. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  3. T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells. Boskovic, G., Niles, R.M. Exp. Cell Res. (2004) [Pubmed]
  4. Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers. Jacobs, J.J., Keblusek, P., Robanus-Maandag, E., Kristel, P., Lingbeek, M., Nederlof, P.M., van Welsem, T., van de Vijver, M.J., Koh, E.Y., Daley, G.Q., van Lohuizen, M. Nat. Genet. (2000) [Pubmed]
  5. Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome. He, M., Wen, L., Campbell, C.E., Wu, J.Y., Rao, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. Carreira, S., Dexter, T.J., Yavuzer, U., Easty, D.J., Goding, C.R. Mol. Cell. Biol. (1998) [Pubmed]
  7. Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Kokubo, H., Tomita-Miyagawa, S., Hamada, Y., Saga, Y. Development (2007) [Pubmed]
  8. The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. Rowley, M., Grothey, E., Couch, F.J. Journal of mammary gland biology and neoplasia. (2004) [Pubmed]
  9. Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Mahlamäki, E.H., Bärlund, M., Tanner, M., Gorunova, L., Höglund, M., Karhu, R., Kallioniemi, A. Genes Chromosomes Cancer (2002) [Pubmed]
  10. Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2. Sinha, S., Abraham, S., Gronostajski, R.M., Campbell, C.E. Gene (2000) [Pubmed]
  11. Identification, characterization, and localization to chromosome 17q21-22 of the human TBX2 homolog, member of a conserved developmental gene family. Law, D.J., Gebuhr, T., Garvey, N., Agulnik, S.I., Silver, L.M. Mamm. Genome (1995) [Pubmed]
  12. Disruption of Scaffold Attachment Factor B1 Leads to TBX2 Up-regulation, Lack of p19ARF Induction, Lack of Senescence, and Cell Immortalization. Dobrzycka, K.M., Kang, K., Jiang, S., Meyer, R., Rao, P.H., Lee, A.V., Oesterreich, S. Cancer Res. (2006) [Pubmed]
  13. Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2. Borke, J.L., Yu, J.C., Isales, C.M., Wagle, N., Do, N.N., Chen, J.R., Bollag, R.J. Annals of plastic surgery. (2003) [Pubmed]
  14. Tbx3 can alter limb position along the rostrocaudal axis of the developing embryo. Rallis, C., Del Buono, J., Logan, M.P. Development (2005) [Pubmed]
  15. Effects of antihistamines on leukotriene and cytokine release from dispersed nasal polyp cells. Küsters, S., Schuligoi, R., Hüttenbrink, K.B., Rudert, J., Wachs, A., Szelenyi, I., Peskar, B.A. Arzneimittel-Forschung. (2002) [Pubmed]
  16. Cell cycle regulation of the T-box transcription factor tbx2. Bilican, B., Goding, C.R. Exp. Cell Res. (2006) [Pubmed]
  17. The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. Lingbeek, M.E., Jacobs, J.J., van Lohuizen, M. J. Biol. Chem. (2002) [Pubmed]
  18. ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriers. Adem, C., Soderberg, C.L., Hafner, K., Reynolds, C., Slezak, J.M., Sinclair, C.S., Sellers, T.A., Schaid, D.J., Couch, F., Hartmann, L.C., Jenkins, R.B. Genes Chromosomes Cancer (2004) [Pubmed]
  19. Virtual cloning and physical mapping of a human T-box gene, TBX4. Yi, C.H., Russ, A., Brook, J.D. Genomics (2000) [Pubmed]
  20. The 17q23 amplicon and breast cancer. Sinclair, C.S., Rowley, M., Naderi, A., Couch, F.J. Breast Cancer Res. Treat. (2003) [Pubmed]
  21. Multiple genes at 17q23 undergo amplification and overexpression in breast cancer. Bärlund, M., Monni, O., Kononen, J., Cornelison, R., Torhorst, J., Sauter, G., Kallioniemi OLLI-P, n.u.l.l., Kallioniemi, A. Cancer Res. (2000) [Pubmed]
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