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Gene Review

TTF2  -  transcription termination factor, RNA...

Homo sapiens

Synonyms: F2, HuF2, Lodestar homolog, RNA polymerase II termination factor, Transcription release factor 2, ...
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Disease relevance of TTF2


Psychiatry related information on TTF2


High impact information on TTF2


Chemical compound and disease context of TTF2


Biological context of TTF2

  • Consistent with a role in termination of all transcription, TTF2 is the only ATP-dependent termination activity associated with Pol II transcription elongation complexes, is largely unaffected by template position, and is impervious to the phosphorylation state of the polymerase [21].
  • Cells in which TTF2 levels are knocked down showed dramatic retention of Ser2 phosphorylated Pol II on mitotic chromosomes and an increase in chromosome segregation defects [21].
  • We find that TTF2 levels rise in the cytoplasm in S and G2 and at the onset of mitosis TTF2 translocates into the nucleus [21].
  • Rescue of the TTF2 knockdown phenotype with an siRNA-resistant replacement vector [22].
  • Transient transfection experiments demonstrate that endogenous TTF2 and GFP-tagged wild-type TTF2 are both sensitive to the siRNA, but GFP-tagged TTF2 encoded by the cDNA containing mismatches is abundantly expressed in the presence of TTF2-siRNA [22].

Anatomical context of TTF2


Associations of TTF2 with chemical compounds


Physical interactions of TTF2


Enzymatic interactions of TTF2

  • The interferon-inducible double-stranded (ds) RNA-activated protein kinase (p68 kinase) is a physiologically important enzyme that regulates the rate of cellular and viral protein synthesis by phosphorylating and thereby inactivating the peptide chain initiation factor 2 [34].
  • Casein kinase-2 phosphorylates serine-2 in the beta-subunit of initiation factor-2 [35].

Co-localisations of TTF2


Regulatory relationships of TTF2


Other interactions of TTF2

  • We examined the role of human TTF2, an RNA polymerase (Pol) I and II termination factor, in mitotic repression of transcription elongation [21].
  • We now show that follicular TG, 27S > 19S > 12S, counter-regulates TSH-increased thyroid-specific gene transcription by suppressing the expression of the TTF-1, TTF-2, and Pax-8 genes [42].
  • Genes associated with thyroid gland dysgenesis include the TSH receptor in non-syndromic congenital hypothyroidism, and Gsalpha and the thyroid transcription factors (TTF-1, TTF-2, and Pax-8), associated with different complex syndromes that include congenital hypothyroidism [43].
  • We suggest that TTF-2 is able to interfere with a specific cofactor required for TTF-1 and Pax-8 activity [37].
  • There were continuous increases in mRNAs for cartilage matrix (proteoglycans and COL2, -9, -10, and -11), receptors [fibroblast growth factor 2 (FGFR2) and parathyroid hormone-related peptide receptor (PTHrP-R)], and transcription factors (SOX5, -6, and -9) as demonstrated by histochemical and microarray assays [44].

Analytical, diagnostic and therapeutic context of TTF2

  • We isolated 17 genes up-regulated by TTF-2, which were subsequently confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) [23].
  • This hypothesis was addressed in the context of muscle regeneration by transplanting satellite cells to muscle laceration sites on a delivery vehicle releasing factors that induce cell activation and migration (hepatocyte growth factor and fibroblast growth factor 2) or transplantation on materials lacking factor release [45].
  • Using blocked design functional MRI and statistical parametric mapping, we investigated the impact of remoteness (factor 1: recent, remote) and emotional valence (factor 2: positive, negative) on the neural correlates of autobiographical memory retrieval [46].
  • Interactions of eukaryotic 5-dimethylaminonaphthalene-1-sulfonyl-initiation factor 2 (eIF-2) from rabbit reticulocytes and the guanine nucleotide exchange factor ( GEF ), Met-tRNAf, GTP, and GDP were monitored by changes in fluorescence anisotropy and radioactive filtration assays [47].
  • UV cross-linking assays followed by immunoprecipitation with anti-SR protein monoclonal antibodies showed that ESEwt, but not mutated ESE RNA, was able to bind both alternative splicing factor/splicing factor 2 and SC35 [48].


  1. A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child. Congdon, T., Nguyen, L.Q., Nogueira, C.R., Habiby, R.L., Medeiros-Neto, G., Kopp, P. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  2. A Novel Missense Mutation in Human TTF-2 (FKHL15) Gene Associated with Congenital Hypothyroidism But Not Athyreosis. Baris, I., Arisoy, A.E., Smith, A., Agostini, M., Mitchell, C.S., Park, S.M., Halefoglu, A.M., Zengin, E., Chatterjee, V.K., Battaloglu, E. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  3. A human RNA polymerase II transcription termination factor is a SWI2/SNF2 family member. Liu, M., Xie, Z., Price, D.H. J. Biol. Chem. (1998) [Pubmed]
  4. Production and application of polyclonal antibody to human thyroid transcription factor 2 reveals thyroid transcription factor 2 protein expression in adult thyroid and hair follicles and prepubertal testis. Sequeira, M., Al-Khafaji, F., Park, S., Lewis, M.D., Wheeler, M.H., Chatterjee, V.K., Jasani, B., Ludgate, M. Thyroid (2003) [Pubmed]
  5. The host protein required for in vitro replication of poliovirus is a protein kinase that phosphorylates eukaryotic initiation factor-2. Morrow, C.D., Gibbons, G.F., Dasgupta, A. Cell (1985) [Pubmed]
  6. Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. Griffin, D.E., Wesselingh, S.L., McArthur, J.C. Ann. Neurol. (1994) [Pubmed]
  7. Cannabinoid receptor gene (CNR1): association with i.v. drug use. Comings, D.E., Muhleman, D., Gade, R., Johnson, P., Verde, R., Saucier, G., MacMurray, J. Mol. Psychiatry (1997) [Pubmed]
  8. Catatonia and mania: patterns of cerebral dysfunction. Abrams, R., Taylor, M.A., Coleman Stolurow, K.A. Biol. Psychiatry (1979) [Pubmed]
  9. The use of pain coping strategies by patients with phantom limb pain. Hill, A. Pain (1993) [Pubmed]
  10. Sequential interactions of fibroblast growth factor-2, brain-derived neurotrophic factor, neurotrophin-3, and their receptors define critical periods in the development of cochlear ganglion cells. Hossain, W.A., Brumwell, C.L., Morest, D.K. Exp. Neurol. (2002) [Pubmed]
  11. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Delépine, M., Nicolino, M., Barrett, T., Golamaully, M., Lathrop, G.M., Julier, C. Nat. Genet. (2000) [Pubmed]
  12. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Clifton-Bligh, R.J., Wentworth, J.M., Heinz, P., Crisp, M.S., John, R., Lazarus, J.H., Ludgate, M., Chatterjee, V.K. Nat. Genet. (1998) [Pubmed]
  13. Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Dever, T.E., Feng, L., Wek, R.C., Cigan, A.M., Donahue, T.F., Hinnebusch, A.G. Cell (1992) [Pubmed]
  14. Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2. Han, A., Pan, F., Stroud, J.C., Youn, H.D., Liu, J.O., Chen, L. Nature (2003) [Pubmed]
  15. Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Mahon, M.J., Donowitz, M., Yun, C.C., Segre, G.V. Nature (2002) [Pubmed]
  16. Translational control mediated by eucaryotic initiation factor-2 is restricted to specific mRNAs in transfected cells. Kaufman, R.J., Murtha, P. Mol. Cell. Biol. (1987) [Pubmed]
  17. Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Matsuda, K., Maruyama, H., Guo, F., Kleeff, J., Itakura, J., Matsumoto, Y., Lander, A.D., Korc, M. Cancer Res. (2001) [Pubmed]
  18. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Hiratsuka, S., Maru, Y., Okada, A., Seiki, M., Noda, T., Shibuya, M. Cancer Res. (2001) [Pubmed]
  19. Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas. Mundhenke, C., Meyer, K., Drew, S., Friedl, A. Am. J. Pathol. (2002) [Pubmed]
  20. Fibroblast growth factor-2 antagonist activity and angiostatic capacity of sulfated Escherichia coli K5 polysaccharide derivatives. Leali, D., Belleri, M., Urbinati, C., Coltrini, D., Oreste, P., Zoppetti, G., Ribatti, D., Rusnati, M., Presta, M. J. Biol. Chem. (2001) [Pubmed]
  21. Involvement of transcription termination factor 2 in mitotic repression of transcription elongation. Jiang, Y., Liu, M., Spencer, C.A., Price, D.H. Mol. Cell (2004) [Pubmed]
  22. Rescue of the TTF2 knockdown phenotype with an siRNA-resistant replacement vector. Jiang, Y., Price, D.H. Cell Cycle (2004) [Pubmed]
  23. TTF-2 stimulates expression of 17 genes, including one novel thyroid-specific gene which might be involved in thyroid development. Hishinuma, A., Ohmika, N., Namatame, T., Ieiri, T. Mol. Cell. Endocrinol. (2004) [Pubmed]
  24. hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing. Leonard, D., Ajuh, P., Lamond, A.I., Legerski, R.J. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. Biological roles of fibroblast growth factor-2. Bikfalvi, A., Klein, S., Pintucci, G., Rifkin, D.B. Endocr. Rev. (1997) [Pubmed]
  26. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. Lotz, M., Jirik, F., Kabouridis, P., Tsoukas, C., Hirano, T., Kishimoto, T., Carson, D.A. J. Exp. Med. (1988) [Pubmed]
  27. Human transcription release factor 2 dissociates RNA polymerases I and II stalled at a cyclobutane thymine dimer. Hara, R., Selby, C.P., Liu, M., Price, D.H., Sancar, A. J. Biol. Chem. (1999) [Pubmed]
  28. Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Shaunak, S., Thomas, S., Gianasi, E., Godwin, A., Jones, E., Teo, I., Mireskandari, K., Luthert, P., Duncan, R., Patterson, S., Khaw, P., Brocchini, S. Nat. Biotechnol. (2004) [Pubmed]
  29. Interleukin 1 regulates heparin-binding growth factor 2 gene expression in vascular smooth muscle cells. Gay, C.G., Winkles, J.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  30. Cloning and characterization of a histone deacetylase, HDAC9. Zhou, X., Marks, P.A., Rifkind, R.A., Richon, V.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  31. Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Grégoire, S., Xiao, L., Nie, J., Zhang, X., Xu, M., Li, J., Wong, J., Seto, E., Yang, X.J. Mol. Cell. Biol. (2007) [Pubmed]
  32. Laminin alpha5 chain metastasis- and angiogenesis-inhibiting peptide blocks fibroblast growth factor 2 activity by binding to the heparan sulfate chains of CD44. Hibino, S., Shibuya, M., Hoffman, M.P., Engbring, J.A., Hossain, R., Mochizuki, M., Kudoh, S., Nomizu, M., Kleinman, H.K. Cancer Res. (2005) [Pubmed]
  33. Direct interaction of Ca2+/calmodulin inhibits histone deacetylase 5 repressor core binding to myocyte enhancer factor 2. Berger, I., Bieniossek, C., Schaffitzel, C., Hassler, M., Santelli, E., Richmond, T.J. J. Biol. Chem. (2003) [Pubmed]
  34. Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. Patel, R.C., Sen, G.C. J. Biol. Chem. (1992) [Pubmed]
  35. Casein kinase-2 phosphorylates serine-2 in the beta-subunit of initiation factor-2. Clark, S.J., Ashford, A.J., Price, N.T., Proud, C.G. Biochim. Biophys. Acta (1989) [Pubmed]
  36. Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors. de Graaf, K., Hekerman, P., Spelten, O., Herrmann, A., Packman, L.C., Büssow, K., Müller-Newen, G., Becker, W. J. Biol. Chem. (2004) [Pubmed]
  37. The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding independent transcriptional repressor. Perrone, L., Pasca di Magliano, M., Zannini, M., Di Lauro, R. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  38. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. Vázquez, F., Hastings, G., Ortega, M.A., Lane, T.F., Oikemus, S., Lombardo, M., Iruela-Arispe, M.L. J. Biol. Chem. (1999) [Pubmed]
  39. Myocyte-specific enhancer binding factor 2C expression in human brain development. Leifer, D., Golden, J., Kowall, N.W. Neuroscience (1994) [Pubmed]
  40. Fibroblast growth factor-2 suppresses oridonin-induced l929 apoptosis through extracellular signal-regulated kinase-dependent and phosphatidylinositol 3-kinase-independent pathway. Huang, J., Wu, L., Tashiro, S., Onodera, S., Ikejima, T. J. Pharmacol. Sci. (2006) [Pubmed]
  41. Tumour suppressor p53 inhibits human fibroblast growth factor 2 expression by a post-transcriptional mechanism. Galy, B., Créancier, L., Zanibellato, C., Prats, A.C., Prats, H. Oncogene (2001) [Pubmed]
  42. Thyroglobulin regulates follicular function and heterogeneity by suppressing thyroid-specific gene expression. Suzuki, K., Mori, A., Lavaroni, S., Ulianich, L., Miyagi, E., Saito, J., Nakazato, M., Pietrarelli, M., Shafran, N., Grassadonia, A., Kim, W.B., Consiglio, E., Formisano, S., Kohn, L.D. Biochimie (1999) [Pubmed]
  43. Genetics of congenital hypothyroidism. Park, S.M., Chatterjee, V.K. J. Med. Genet. (2005) [Pubmed]
  44. In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Sekiya, I., Vuoristo, J.T., Larson, B.L., Prockop, D.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  45. Regulating activation of transplanted cells controls tissue regeneration. Hill, E., Boontheekul, T., Mooney, D.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  46. Differential remoteness and emotional tone modulate the neural correlates of autobiographical memory. Piefke, M., Weiss, P.H., Zilles, K., Markowitsch, H.J., Fink, G.R. Brain (2003) [Pubmed]
  47. Studies on the role of eukaryotic nucleotide exchange factor in polypeptide chain initiation. Goss, D.J., Parkhurst, L.J., Mehta, H.B., Woodley, C.L., Wahba, A.J. J. Biol. Chem. (1984) [Pubmed]
  48. An exonic splicing enhancer offsets the atypical GU-rich 3' splice site of human apolipoprotein A-II exon 3. Arrisi-Mercado, P., Romano, M., Muro, A.F., Baralle, F.E. J. Biol. Chem. (2004) [Pubmed]
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