CDX2
From Wikipedia, the free encyclopedia
Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene.[1][1] The protein encoded by this gene is a homeobox transcription factor.
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 President's Council on Bioethics, as a solution to the stem cell controversy.[7] According to one of the plans put forth, by deactivating the gene, it would not be possible for a properly organized embryo to form, thus providing stem cells without requiring the destruction of an embryo.[8] Other genes that have been proposed for this purpose include Hnf4, which is required for gastrulation.[7][9]
Interactions
CDX2 has been shown to interact with EP300,[10] CREB binding protein[11] and PAX6.[10]
References
- ↑ 1.0 1.1 German MS, Wang J, Fernald AA, Espinosa R 3rd, 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. doi:10.1006/geno.1994.1639. PMID 7698771.
- ↑ 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. doi:10.1073/pnas.0401654101. PMC 419659. PMID 15136723.
- ↑ 3.0 3.1 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. doi:10.1073/pnas.0305555101. PMC 321764. PMID 14718672.
- ↑ 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. doi:10.1172/JCI30182. PMC 1810574. PMID 17347684.
- ↑ 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. doi:10.1053/j.gastro.2005.12.032. PMID 16618413.
- ↑ 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. doi:10.1038/modpathol.3800968. PMID 17906616.
- ↑ 7.0 7.1 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.
- ↑ Saletan W (2004-12-06). "The creepy solution to the stem-cell debate". Slate Magazine. Retrieved 2008-07-16.
- ↑ Hurlbut WB (2007). "Ethics and embryonic stem cell research: altered nuclear transfer as a way forward". BioDrugs 21 (2): 79–83. PMID 17402791.
- ↑ 10.0 10.1 Hussain, M A; Habener J F (Oct 1999). "Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator". J. Biol. Chem. (UNITED STATES) 274 (41): 28950–7. doi:10.1074/jbc.274.41.28950. ISSN 0021-9258. PMID 10506141.
- ↑ Lorentz, O; Suh E R, Taylor J K, Boudreau F, Traber P G (Mar 1999). "CREB-binding [corrected] protein interacts with the homeodomain protein Cdx2 and enhances transcriptional activity". J. Biol. Chem. (UNITED STATES) 274 (11): 7196–9. doi:10.1074/jbc.274.11.7196. ISSN 0021-9258. PMID 10066780. (Retracted. If this is intentional, please replace
{{Retracted}}with{{Retracted|intentional=yes}}.)
Further reading
- 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. PMC 359269. PMID 7935448.
- Inoue H, Riggs AC, Tanizawa Y, et al. (1996). "Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene". Diabetes 45 (6): 789–94. doi:10.2337/diabetes.45.6.789. PMID 8635654.
- Mallo GV, Rechreche H, Frigerio JM, et al. (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. doi:10.1002/(SICI)1097-0215(19970220)74:1<35::AID-IJC7>3.0.CO;2-1. PMID 9036867.
- Chawengsaksophak K, James R, Hammond VE, et al. (1997). "Homeosis and intestinal tumours in Cdx2 mutant mice". Nature 386 (6620): 84–7. doi:10.1038/386084a0. PMID 9052785.
- Walters JR, Howard A, Rumble HE, et al. (1997). "Differences in expression of homeobox transcription factors in proximal and distal human small intestine". Gastroenterology 113 (2): 472–7. doi:10.1053/gast.1997.v113.pm9247466. PMID 9247466.
- 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. doi:10.1046/j.1469-1809.1997.6150393.x. PMID 9459001.
- Yamamoto H, Miyamoto K, Li B, et al. (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. doi:10.1359/jbmr.1999.14.2.240. PMID 9933478.
- 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. doi:10.1074/jbc.274.41.28950. PMID 10506141.
- Mitchelmore C, Troelsen JT, Spodsberg N, et al. (2000). "Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene". Biochem. J. 346 (2): 529–35. doi:10.1042/0264-6021:3460529. PMC 1220882. PMID 10677375.
- Sivagnanasundaram S, Islam I, Talbot I, et al. (2001). "The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis". Br. J. Cancer 84 (2): 218–25. doi:10.1054/bjoc.2000.1544. PMC 2363702. PMID 11161380.
- Rings EH, Boudreau F, Taylor JK, et al. (2001). "Phosphorylation of the serine 60 residue within the Cdx2 activation domain mediates its transactivation capacity". Gastroenterology 121 (6): 1437–50. doi:10.1053/gast.2001.29618. PMID 11729123.
- Hinoi T, Tani M, Lucas PC, et al. (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. doi:10.1016/S0002-9440(10)63074-X. PMC 1850596. PMID 11733373.
- Mizoshita T, Inada K, Tsukamoto T, et al. (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. doi:10.1007/PL00011741. PMID 11846061.
- Eda A, Osawa H, Yanaka I, et al. (2002). "Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia". J. Gastroenterol. 37 (2): 94–100. doi:10.1007/s005350200002. PMID 11871772.
- 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. doi:10.1136/gut.51.2.184. PMC 1773308. PMID 12117877.
- Moucadel V, Totaro MS, Dell CD, et al. (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. doi:10.1016/S0006-291X(02)02250-7. PMID 12270138.
- Strausberg RL, Feingold EA, Grouse LH, et al. (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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Song BL, Qi W, Wang CH, et al. (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. PMID 12518221.
External links
- CDX2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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