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Transcription factor 7-like 2 (T-cell specific, HMG-box)

PDB rendering based on 1jdh.
Available structures
1jdh, 1jpw, 2gl7, 2lef
Identifiers
Symbols TCF7L2; TCF4; TCF-4
External IDs OMIM602228 MGI1202879 HomoloGene7564 GeneCards: TCF7L2 Gene
RNA expression pattern
PBB GE TCF7L2 212759 s at tn.png
PBB GE TCF7L2 212761 at tn.png
PBB GE TCF7L2 212762 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6934 21416
Ensembl ENSG00000148737 ENSMUSG00000024985
UniProt Q9NQB0 Q80WT9
RefSeq (mRNA) NM_030756 NM_009333
RefSeq (protein) NP_110383 NP_033359
Location (UCSC) Chr 10:
114.7 - 114.92 Mb
Chr 19:
55.8 - 55.99 Mb
PubMed search [1] [2]

Transcription factor 7-like 2 (T-cell specific, HMG-box) also known as TCF7L2 or TCF4 is a protein acting as a transcription factor. In humans this protein is encoded by the TCF7L2 gene.[1][2] A variant of the protein is linked to higher risk to develop type 2 diabetes.[3]

Structure of complex between TCF7L2 (orange), β-catenin (red), and BCL9 (brown).[4]

Contents

Function

TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions in the cell. It is a member of the Wnt signaling pathway. Stimulation of the pathway leads to the association of β-catenin with TCF7L2 and BCL9 in the nucleus, which in turn results in the activation of Wnt target genes.[3]

Disease implications

TCF7L2 is implicated in a large variety of diseases. Several single nucleotide polymorphisms are associated with type 2 diabetes. In European populations it was found to be a major determinant of type 2 risk.[3]

A frameshift mutation of TCF7L2 is implicated in colorectal cancer.[5][6] Variants of the gene are most likely involved in many other cancer types.[7]

Name confusion

While TCF4 is sometimes used as an alias symbol for TCF7L2, it is also the symbol officially approved by the HUGO Gene Nomenclature Committee for the transcription factor 4 gene.

References

  1. ^ "Entrez Gene: TCF7L2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6934.  
  2. ^ Castrop J, van Norren K, Clevers H (February 1992). "A gene family of HMG-box transcription factors with homology to TCF-1". Nucleic Acids Res. 20 (3): 611. doi:10.1093/nar/20.3.611. PMID 1741298. PMC 310434. http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=1741298.  
  3. ^ a b c Jin T, Liu L (November 2008). "The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus". Mol. Endocrinol. 22 (11): 2383–92. doi:10.1210/me.2008-0135. PMID 18599616.  
  4. ^ PDB 2GL7; Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W (October 2006). "Crystal structure of a beta-catenin/BCL9/Tcf4 complex". Mol. Cell 24 (2): 293–300. doi:10.1016/j.molcel.2006.09.001. PMID 17052462.  
  5. ^ Slattery ML, Folsom AR, Wolff R, Herrick J, Caan BJ, Potter JD (April 2008). "Transcription factor 7-like 2 polymorphism and colon cancer". Cancer Epidemiol. Biomarkers Prev. 17 (4): 978–82. doi:10.1158/1055-9965.EPI-07-2687. PMID 18398040.  
  6. ^ Hazra A, Fuchs CS, Chan AT, Giovannucci EL, Hunter DJ (November 2008). "Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk". Cancer Causes Control 19 (9): 975–80. doi:10.1007/s10552-008-9164-3. PMID 18478343.  
  7. ^ Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L (July 2008). "A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer". Proc. Natl. Acad. Sci. U.S.A. 105 (28): 9697–702. doi:10.1073/pnas.0804709105. PMID 18621708.  

Further reading

  • Segditsas S, Tomlinson I (2007). "Colorectal cancer and genetic alterations in the Wnt pathway.". Oncogene 25 (57): 7531–7. doi:10.1038/sj.onc.1210059. PMID 17143297.  
  • Florez JC (2007). "The new type 2 diabetes gene TCF7L2.". Current opinion in clinical nutrition and metabolic care 10 (4): 391–6. doi:10.1097/MCO.0b013e3281e2c9be. PMID 17563454.  
  • Castrop J, van Norren K, Clevers H (1992). "A gene family of HMG-box transcription factors with homology to TCF-1.". Nucleic Acids Res. 20 (3): 611. doi:10.1093/nar/20.3.611. PMID 1741298.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.  
  • Korinek V, Barker N, Morin PJ, et al. (1997). "Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.". Science 275 (5307): 1784–7. doi:10.1126/science.275.5307.1784. PMID 9065401.  
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.  
  • He TC, Sparks AB, Rago C, et al. (1998). "Identification of c-MYC as a target of the APC pathway.". Science 281 (5382): 1509–12. doi:10.1126/science.281.5382.1509. PMID 9727977.  
  • Barker N, Huls G, Korinek V, Clevers H (1999). "Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium.". Am. J. Pathol. 154 (1): 29–35. PMID 9916915.  
  • Omer CA, Miller PJ, Diehl RE, Kral AM (1999). "Identification of Tcf4 residues involved in high-affinity beta-catenin binding.". Biochem. Biophys. Res. Commun. 256 (3): 584–90. doi:10.1006/bbrc.1999.0379. PMID 10080941.  
  • Giannini AL, Vivanco MM, Kypta RM (2000). "Analysis of beta-catenin aggregation and localization using GFP fusion proteins: nuclear import of alpha-catenin by the beta-catenin/Tcf complex.". Exp. Cell Res. 255 (2): 207–20. doi:10.1006/excr.1999.4785. PMID 10694436.  
  • Duval A, Busson-Leconiat M, Berger R, Hamelin R (2000). "Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3.". Cytogenet. Cell Genet. 88 (3-4): 264–5. doi:10.1159/000015534. PMID 10828605.  
  • Duval A, Rolland S, Tubacher E, et al. (2000). "The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.". Cancer Res. 60 (14): 3872–9. PMID 10919662.  
  • Brantjes H, Roose J, van De Wetering M, Clevers H (2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors.". Nucleic Acids Res. 29 (7): 1410–9. doi:10.1093/nar/29.7.1410. PMID 11266540.  
  • Palacino JJ, Murphy MP, Murayama O, et al. (2001). "Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion.". J. Biol. Chem. 276 (42): 38563–9. doi:10.1074/jbc.M105376200. PMID 11504726.  
  • Miravet S, Piedra J, Miró F, et al. (2002). "The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin.". J. Biol. Chem. 277 (3): 1884–91. doi:10.1074/jbc.M110248200. PMID 11711551.  
  • Graham TA, Ferkey DM, Mao F, et al. (2002). "Tcf4 can specifically recognize beta-catenin using alternative conformations.". Nat. Struct. Biol. 8 (12): 1048–52. doi:10.1038/nsb718. PMID 11713475.  
  • Poy F, Lepourcelet M, Shivdasani RA, Eck MJ (2002). "Structure of a human Tcf4-beta-catenin complex.". Nat. Struct. Biol. 8 (12): 1053–7. doi:10.1038/nsb720. PMID 11713476.  
  • Thiele A, Wasner M, Müller C, et al. (2001). "Regulation and possible function of beta-catenin in human monocytes.". J. Immunol. 167 (12): 6786–93. PMID 11739494.  
  • Marchenko GN, Marchenko ND, Leng J, Strongin AY (2002). "Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin.". Biochem. J. 363 (Pt 2): 253–62. doi:10.1042/0264-6021:3630253. PMID 11931652.  
  • Leung JY, Kolligs FT, Wu R, et al. (2002). "Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.". J. Biol. Chem. 277 (24): 21657–65. doi:10.1074/jbc.M200139200. PMID 11940574.  

External links

  • TCF7L2 here called TCF4 features on this Wnt pathway web site: Wnt signalling molecules TCFs
  • Structure determination of TCF7L2: PDB entry 2GL7 and related publication on PubMed
  • PubMed GeneRIFs (summaries of related scientific publications) - [3]
  • Weizmann Institute GeneCard for TCF7L2
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