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Cdx2

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Title: Cdx2  
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Subject: Homeobox, Cdx protein family, Human genes, Transcription factors, Human embryogenesis
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Cdx2

Caudal type homeobox 2
Identifiers
Symbols  ; CDX-3; CDX3
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

CDX-2 is a homeobox gene that encodes the CDX-2 protein - a transcription factor expressed in the nuclei of intestinal epithelial cells.[1]

Contents

  • Function 1
  • Biomarker for intestinal cancer 2
  • Possible use in stem cell research 3
  • Interactions 4
  • References 5
  • Further reading 6
  • External links 7

Function

Cdx2 is the gene that directs early embryogenesis in mice. It is required to form the placenta.[2]

Ectopic expression of CDX2 was reported more than 85% of the human patients with Acute myeloid leukemia (AML). Ectopic expression of Cdx2 in murine bone marrow induced AML in mice and upregulate Hox genes in bone marrow progenitors.[3][3][4] CDX2 is also implicated in the pathogenesis of Barrett's esophagus were it has been shown that components from gastroesofageal reflux such as bile acids are able to induce the expression of an intestinal differentiation program through up-regulation of NF-κB and CDX2.[5]

Biomarker for intestinal cancer

CDX2 is also used in diagnostic surgical pathology as a marker for gastrointestinal differentiation, especially colorectal.[6]

Possible use in stem cell research

This gene (or, more specifically, the equivalent gene in humans) has come up in the proposal by the


External links

  • Suh E, Chen L, Taylor J, Traber PG (1994). "A homeodomain protein related to caudal regulates intestine-specific gene transcription". Mol. Cell. Biol. 14 (11): 7340–51.  
  • Inoue H, Riggs AC, Tanizawa Y, Ueda K, Kuwano A, Liu L, Donis-Keller H, Permutt MA (1996). "Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene". Diabetes 45 (6): 789–94.  
  • Mallo GV, Rechreche H, Frigerio JM, Rocha D, Zweibaum A, Lacasa M, Jordan BR, Dusetti NJ, Dagorn JC, Iovanna JL (1997). "Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis". Int. J. Cancer 74 (1): 35–44.  
  • Chawengsaksophak K, James R, Hammond VE, Köntgen F, Beck F (1997). "Homeosis and intestinal tumours in Cdx2 mutant mice". Nature 386 (6620): 84–7.  
  • Walters JR, Howard A, Rumble HE, Prathalingam SR, Shaw-Smith CJ, Legon S (1997). "Differences in expression of homeobox transcription factors in proximal and distal human small intestine". Gastroenterology 113 (2): 472–7.  
  • Drummond F, Putt W, Fox M, Edwards YH (1998). "Cloning and chromosome assignment of the human CDX2 gene". Ann. Hum. Genet. 61 (Pt 5): 393–400.  
  • Yamamoto H, Miyamoto K, Li B, Taketani Y, Kitano M, Inoue Y, Morita K, Pike JW, Takeda E (1999). "The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine". J. Bone Miner. Res. 14 (2): 240–7.  
  • Hussain MA, Habener JF (1999). "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator". J. Biol. Chem. 274 (41): 28950–7.  
  • Mitchelmore C, Troelsen JT, Spodsberg N, Sjöström H, Norén O (2000). "Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene". Biochem. J. 346 (2): 529–35.  
  • Sivagnanasundaram S, Islam I, Talbot I, Drummond F, Walters JR, Edwards YH (2001). "The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis". Br. J. Cancer 84 (2): 218–25.  
  • Rings EH, Boudreau F, Taylor JK, Moffett J, Suh ER, Traber PG (2001). "Phosphorylation of the serine 60 residue within the Cdx2 activation domain mediates its transactivation capacity". Gastroenterology 121 (6): 1437–50.  
  • Hinoi T, Tani M, Lucas PC, Caca K, Dunn RL, Macri E, Loda M, Appelman HD, Cho KR, Fearon ER (2001). "Loss of CDX2 Expression and Microsatellite Instability Are Prominent Features of Large Cell Minimally Differentiated Carcinomas of the Colon". Am. J. Pathol. 159 (6): 2239–48.  
  • Mizoshita T, Inada K, Tsukamoto T, Kodera Y, Yamamura Y, Hirai T, Kato T, Joh T, Itoh M, Tatematsu M (2002). "Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa—with special emphasis on participation in intestinal metaplasia of the human stomach". Gastric Cancer 4 (4): 185–91.  
  • Eda A, Osawa H, Yanaka I, Satoh K, Mutoh H, Kihira K, Sugano K (2002). "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia". J. Gastroenterol. 37 (2): 94–100.  
  • Qualtrough D, Hinoi T, Fearon E, Paraskeva C (2002). "Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system". Gut 51 (2): 184–90.  
  • Moucadel V, Totaro MS, Dell CD, Soubeyran P, Dagorn JC, Freund JN, Iovanna JL (2002). "The homeobox gene Cdx1 belongs to the p53-p21(WAF)-Bcl-2 network in intestinal epithelial cells". Biochem. Biophys. Res. Commun. 297 (3): 607–15.  
  • Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.  
  • Song BL, Qi W, Wang CH, Yang JB, Yang XY, Lin ZX, Li BL (2003). "Preparation of an anti-Cdx-2 antibody for analysis of different species Cdx-2 binding to acat2 promoter". Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35 (1): 6–12.  

Further reading

  1. ^ German MS, Wang J, Fernald AA, Espinosa R, Le Beau MM, Bell GI (May 1995). "Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13". Genomics 24 (2): 403–4.  
  2. ^ Chawengsaksophak K, de Graaff W, Rossant J, Deschamps J, Beck F (May 2004). "Cdx2 is essential for axial elongation in mouse development". Proc. Natl. Acad. Sci. U.S.A. 101 (20): 7641–5.  
  3. ^ a b Rawat VP, Cusan M, Deshpande A, Hiddemann W, Quintanilla-Martinez L, Humphries RK, Bohlander SK, Feuring-Buske M, Buske C (January 2004). "Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia". Proc. Natl. Acad. Sci. U.S.A. 101 (3): 817–22.  
  4. ^ Scholl C, Bansal D, Döhner K, Eiwen K, Huntly BJ, Lee BH, Rücker FG, Schlenk RF, Bullinger L, Döhner H, Gilliland DG, Fröhling S (April 2007). "The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis". J. Clin. Invest. 117 (4): 1037–48.  
  5. ^ Debruyne PR, Witek M, Gong L, Birbe R, Chervoneva I, Jin T, Domon-Cell C, Palazzo JP, Freund JN, Li P, Pitari GM, Schulz S, Waldman SA (April 2006). "Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through nuclear factor-kappaB and Cdx2 in human esophageal cells". Gastroenterology 130 (4): 1191–206.  
  6. ^ Liu Q, Teh M, Ito K, Shah N, Ito Y, Yeoh KG (December 2007). "CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer". Mod. Pathol. 20 (12): 1286–97.  
  7. ^ a b Hurlbut WB (2004). "Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells". The President's Council on Bioethics. The White House of the United States of America. Retrieved 2008-07-16. 
  8. ^ Saletan W (2004-12-06). "The creepy solution to the stem-cell debate". Slate Magazine. Retrieved 2008-07-16. 
  9. ^ Hurlbut WB (2007). "Ethics and embryonic stem cell research: altered nuclear transfer as a way forward". BioDrugs 21 (2): 79–83.  
  10. ^ a b Hussain MA, Habener JF (Oct 1999). "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator". J. Biol. Chem. 274 (41): 28950–7.  

References

CDX2 has been shown to interact with EP300,[10] and PAX6.[10]

Interactions

[9][7].gastrulation, which is required for Hnf4 Other genes that have been proposed for this purpose include [8]

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