TCF7L2

TCF7L2 also known as TCF4 is a protein acting as a transcription factor. A variant of the protein is linked to higher risk to develop type 2 diabetes.

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.

Disease implications

TCF7L2 is implied 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.

A frameshift mutation of TCF7L2 is implied in colorectal cancer. Variants of the gene are most likely involved in many other cancer types. See PubMed GeneRIFs for more information [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=gene_full_report&db=gene&cmd=Display&dopt=gene_pubmed_rif&from_uid=6934] .

Further reading

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

Extgernal links

* TCF7L2 here called TCF4 features on this Wnt pathway web site: [http://www.stanford.edu/~rnusse/pathways/cell2.html Wnt signalling molecules] [http://www.stanford.edu/~rnusse/axindshtcf/tcf2.html TCFs]
* Structure determination of TCF7L2: [http://www.rcsb.org/pdb/explore.do?structureId=2GL7 PDB entry 2GL7] and related publication on [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Crystal%20Structure%20of%20a%20beta-Catenin/BCL9/Tcf4%20Complex PubMed]
* PubMed GeneRIFs (summaries of related scientific publications) - [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=gene_full_report&db=gene&cmd=Display&dopt=gene_pubmed_rif&from_uid=6934]
* Weizmann Institute GeneCard for [http://www.genecards.org/cgi-bin/carddisp.pl?gene=TCF7L2&search=tcf7l2 TCF7L2]

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