Download Gene Section TFF3 (trefoil factor 3 (intestinal)) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
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Gene Section
Mini Review
TFF3 (trefoil factor 3 (intestinal))
Catherine Tomasetto
I.G.B.M.C., BP 163, 1 rue Laurent Fries, 67404 Illkirch, France (CT)
Published in Atlas Database: March 2001
Online updated version : http://AtlasGeneticsOncology.org/Genes/TFF3ID265.html
DOI: 10.4267/2042/37730
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2001 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Function
Identity
Description
TFF3 promotes migration of epithelial cells in vitro and
enhance mucosal healing and epithelial restitutions in
vivo in the gastrointestinal mucosa. TFF3 deficient
mice aresuceptible to colonic injury induced by
standard agents and restitution is impaired. In addition
TFF3 deficient mice have an increase in colonocyte
apoptosis. The protective action of TFF3 involves
activation of both EGF-R and PI3K-Akt pathways. The
role of TFF3 in the brain is not clear yet.
3.3 kb gene, 3 exons.
Homology
Transcription
TFF3 belongs to the Trefoil peptide family (TFF) and
possesse one TFF1 motif homologous to the TFF motif
of TFF1 and TFF2. The TFF motif spans about 40
amino acids and is formed by 6 conserved cysteines
residues involved in specific disulfites bridges.
Other names: ITF (Intestinal Trefoil Factor)
HGNC (Hugo): TFF3
Location: 21q22.3
Local order: Belongs to the TFF cluster.
DNA/RNA
600 bp.
Protein
Description
Implicated in
precursor 74 amino acids, mature peptide 51
aminoacids, trefoil domain from aminoacids residues
24 to 67. The 74 aminoacids TFF3 protein precusor
contains a signal peptide. The mature secreted peptide
of 51 aminoacids contains one TFF (TreFoil Factor)
domain and one acidic C-terminal domain. The acidic
C-terminal domain contains a free cystein residue that
promotes homodimerization and heterodimerization.
Inflamatory bowel diseases, TFF3 is expressed in
cancer cells derived from the gastrointestinal tract, in
hepatocellular carcinoma cells and in small cell lung
carcinoma cells. Like TFF1, TFF3 is expressed in
oestrogen-responsive breast cancer cell line and is
expressed in breast cancer.
References
Expression
Hauser F, Poulsom R, Chinery R, Rogers LA, Hanby AM,
Wright NA, Hoffmann W. hP1.B, a human P-domain peptide
homologous with rat intestinal trefoil factor, is expressed also
in the ulcer-associated cell lineage and the uterus. Proc Natl
Acad Sci U S A. 1993 Aug 1;90(15):6961-5
Under normal conditions TFF3 is expressed by gobblet
cell of the intesine and the colon. TFF3 expression was
found in human respiratory tract, human conjunctival
goblet cells and in human salivarygland. In addition
TFF3 peptive was found in human hypothalamus.
Semenkovich CF, Coleman T, Goforth R. Physiologic
concentrations of glucose regulate fatty acid synthase activity
in HepG2 cells by mediating fatty acid synthase mRNA
stability. J Biol Chem. 1993 Apr 5;268(10):6961-70
Localisation
In secreterory epithelia TFF3 is expressed by mucinproducing cells. In the brain TFF3 is expressed by a
population of neurons of the human hypothamic
paraventricular and supraoptic nuclei.
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(2)
Chinery R, Bates PA, De A, Freemont PS. Characterisation of
the single copy trefoil peptides intestinal trefoil factor and pS2
114
TFF3 trefoil factor 3 (intestinal)
Tomasetto C
and their ability to form covalent dimers. FEBS Lett. 1995 Jan
2;357(1):50-4
human colon carcinoma cells. Proc Natl Acad Sci U S A. 1998
Mar 17;95(6):3122-7
Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky
DK. Trefoil peptide protection of intestinal epithelial barrier
function: cooperative interaction with mucin glycoprotein.
Gastroenterology. 1995 Aug;109(2):516-23
Kanai M, Mullen C, Podolsky DK. Intestinal trefoil factor
induces inactivation of extracellular signal-regulated protein
kinase in intestinal epithelial cells. Proc Natl Acad Sci U S A.
1998 Jan 6;95(1):178-82
Babyatsky MW, deBeaumont M, Thim L, Podolsky DK. Oral
trefoil peptides protect against ethanol- and indomethacininduced gastric injury in rats. Gastroenterology. 1996
Feb;110(2):489-97
Langer G, Jagla W, Behrens-Baumann W, Walter S, Hoffmann
W. Secretory peptides TFF1 and TFF3 synthesized in human
conjunctival goblet cells. Invest Ophthalmol Vis Sci. 1999
Sep;40(10):2220-4
Mashimo H, Wu DC, Podolsky DK, Fishman MC. Impaired
defense of intestinal mucosa in mice lacking intestinal trefoil
factor. Science. 1996 Oct 11;274(5285):262-5
Wiede A, Jagla W, Welte T, Köhnlein T, Busk H, Hoffmann W.
Localization of TFF3, a new mucus-associated peptide of the
human respiratory tract. Am J Respir Crit Care Med. 1999
Apr;159(4 Pt 1):1330-5
Sands BE, Podolsky DK. The trefoil peptide family. Annu Rev
Physiol. 1996;58:253-73
Jagla W, Wiede A, Dietzmann K, Rutkowski K, Hoffmann W.
Co-localization of TFF3 peptide and oxytocin in the human
hypothalamus. FASEB J. 2000 Jun;14(9):1126-31
May FE, Westley BR. Expression of human intestinal trefoil
factor in malignant cells and its regulation by oestrogen in
breast cancer cells. J Pathol. 1997 Aug;182(4):404-13
Kinoshita K, Taupin DR, Itoh H, Podolsky DK. Distinct
pathways of cell migration and antiapoptotic response to
epithelial injury: structure-function analysis of human intestinal
trefoil factor. Mol Cell Biol. 2000 Jul;20(13):4680-90
Poulsom R, Hanby AM, Lalani EN, Hauser F, Hoffmann W,
Stamp GW. Intestinal trefoil factor (TFF 3) and pS2 (TFF 1),
but not spasmolytic polypeptide (TFF 2) mRNAs are coexpressed in normal, hyperplastic, and neoplastic human
breast epithelium. J Pathol. 1997 Sep;183(1):30-8
Podolsky DK. Mechanisms of regulatory peptide action in the
gastrointestinal tract: trefoil peptides. J Gastroenterol. 2000;35
Suppl 12:69-74
Seib T, Blin N, Hilgert K, Seifert M, Theisinger B, Engel M,
Dooley S, Zang KD, Welter C. The three human trefoil genes
TFF1, TFF2, and TFF3 are located within a region of 55 kb on
chromosome 21q22.3. Genomics. 1997 Feb 15;40(1):200-2
Taupin DR, Kinoshita K, Podolsky DK. Intestinal trefoil factor
confers colonic epithelial resistance to apoptosis. Proc Natl
Acad Sci U S A. 2000 Jan 18;97(2):799-804
Thim L. Trefoil peptides: from structure to function. Cell Mol
Life Sci. 1997 Dec;53(11-12):888-903
This article should be referenced as such:
Tomasetto C. TFF3 (trefoil factor 3 (intestinal)). Atlas Genet
Cytogenet Oncol Haematol. 2001; 5(2):114-115.
Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari
A, Hattori T, Wright NA, Bodmer WF, Pignatelli M. Intestinal
trefoil factor controls the expression of the adenomatous
polyposis coli-catenin and the E-cadherin-catenin complexes in
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(2)
115