CDX2

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View/Edit Human

Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. This gene is a member of the caudal-related homeobox transcription factor family that is expressed in the nuclei of intestinal epithelial cells.^[1]

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 in 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 where it has been shown that components from gastroesophageal 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] and PAX6.^[10]

References

↑ German MS, Wang J, Fernald AA, Espinosa R, Le Beau MM, Bell GI (Nov 1994). "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". Proceedings of the National Academy of Sciences of the United States of America. 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 (Jan 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". Proceedings of the National Academy of Sciences of the United States of America. 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 (Apr 2007). "The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis". The Journal of Clinical Investigation. 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 (Apr 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 (Dec 2007). "CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer". Modern Pathology. 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. Archived from the original on May 17, 2008. Retrieved 2008-07-16.
↑ Saletan, William (2004-12-06). "The creepy solution to the stem-cell debate". Slate. Archived from the original on February 14, 2007. 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. doi:10.2165/00063030-200721020-00002. PMID 17402791.
↑ ^10.0 ^10.1 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". The Journal of Biological Chemistry. 274 (41): 28950–7. doi:10.1074/jbc.274.41.28950. PMID 10506141.

Suh E, Chen L, Taylor J, Traber PG (Nov 1994). "A homeodomain protein related to caudal regulates intestine-specific gene transcription". Molecular and Cellular Biology. 14 (11): 7340–51. doi:10.1128/mcb.14.11.7340. PMC 359269. PMID 7935448.
Inoue H, Riggs AC, Tanizawa Y, Ueda K, Kuwano A, Liu L, Donis-Keller H, Permutt MA (Jun 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, Rocha D, Zweibaum A, Lacasa M, Jordan BR, Dusetti NJ, Dagorn JC, Iovanna JL (Feb 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". International Journal of 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, Köntgen F, Beck F (Mar 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, Prathalingam SR, Shaw-Smith CJ, Legon S (Aug 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 (Sep 1997). "Cloning and chromosome assignment of the human CDX2 gene". Annals of Human Genetics. 61 (Pt 5): 393–400. doi:10.1046/j.1469-1809.1997.6150393.x. PMID 9459001.
Yamamoto H, Miyamoto K, Li B, Taketani Y, Kitano M, Inoue Y, Morita K, Pike JW, Takeda E (Feb 1999). "The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine". Journal of Bone and Mineral Research. 14 (2): 240–7. doi:10.1359/jbmr.1999.14.2.240. PMID 9933478.
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". The Journal of Biological Chemistry. 274 (41): 28950–7. doi:10.1074/jbc.274.41.28950. PMID 10506141.
Mitchelmore C, Troelsen JT, Spodsberg N, Sjöström H, Norén O (Mar 2000). "Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene". The Biochemical Journal. 346 (2): 529–35. doi:10.1042/0264-6021:3460529. PMC 1220882. PMID 10677375.
Sivagnanasundaram S, Islam I, Talbot I, Drummond F, Walters JR, Edwards YH (Jan 2001). "The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis". British Journal of Cancer. 84 (2): 218–25. doi:10.1054/bjoc.2000.1544. PMC 2363702. PMID 11161380.
Rings EH, Boudreau F, Taylor JK, Moffett J, Suh ER, Traber PG (Dec 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, Caca K, Dunn RL, Macri E, Loda M, Appelman HD, Cho KR, Fearon ER (Dec 2001). "Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon". The American Journal of Pathology. 159 (6): 2239–48. doi:10.1016/S0002-9440(10)63074-X. PMC 1850596. PMID 11733373.
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. doi:10.1007/PL00011741. PMID 11846061.
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". Journal of Gastroenterology. 37 (2): 94–100. doi:10.1007/s005350200002. PMID 11871772.
Qualtrough D, Hinoi T, Fearon E, Paraskeva C (Aug 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, Soubeyran P, Dagorn JC, Freund JN, Iovanna JL (Sep 2002). "The homeobox gene Cdx1 belongs to the p53-p21(WAF)-Bcl-2 network in intestinal epithelial cells". Biochemical and Biophysical Research Communications. 297 (3): 607–15. doi:10.1016/S0006-291X(02)02250-7. PMID 12270138.
Song BL, Qi W, Wang CH, Yang JB, Yang XY, Lin ZX, Li BL (Jan 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 Acta Biochimica et Biophysica Sinica. 35 (1): 6–12. PMID 12518221.

External links

CDX2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Human CDX2 genome location and CDX2 gene details page in the UCSC Genome Browser.

[pmid7698771-1] German MS, Wang J, Fernald AA, Espinosa R, Le Beau MM, Bell GI (Nov 1994). "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.

[pmid15136723-2] Chawengsaksophak K, de Graaff W, Rossant J, Deschamps J, Beck F (May 2004). "Cdx2 is essential for axial elongation in mouse development". Proceedings of the National Academy of Sciences of the United States of America. 101 (20): 7641–5. doi:10.1073/pnas.0401654101. PMC 419659. PMID 15136723.

[Rawat_2004-3] 3.0 ^3.1 Rawat VP, Cusan M, Deshpande A, Hiddemann W, Quintanilla-Martinez L, Humphries RK, Bohlander SK, Feuring-Buske M, Buske C (Jan 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". Proceedings of the National Academy of Sciences of the United States of America. 101 (3): 817–22. doi:10.1073/pnas.0305555101. PMC 321764. PMID 14718672.

[Scholl_2007-4] Scholl C, Bansal D, Döhner K, Eiwen K, Huntly BJ, Lee BH, Rücker FG, Schlenk RF, Bullinger L, Döhner H, Gilliland DG, Fröhling S (Apr 2007). "The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis". The Journal of Clinical Investigation. 117 (4): 1037–48. doi:10.1172/JCI30182. PMC 1810574. PMID 17347684.

[Debruyne_2006-5] 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 (Apr 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.

[pmid17906616-6] Liu Q, Teh M, Ito K, Shah N, Ito Y, Yeoh KG (Dec 2007). "CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer". Modern Pathology. 20 (12): 1286–97. doi:10.1038/modpathol.3800968. PMID 17906616.

[url_Bioethics-7] 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. Archived from the original on May 17, 2008. Retrieved 2008-07-16.

[Slate_url-8] Saletan, William (2004-12-06). "The creepy solution to the stem-cell debate". Slate. Archived from the original on February 14, 2007. Retrieved 2008-07-16.

[pmid17402791-9] Hurlbut WB (2007). "Ethics and embryonic stem cell research: altered nuclear transfer as a way forward". BioDrugs. 21 (2): 79–83. doi:10.2165/00063030-200721020-00002. PMID 17402791.

[pmid10506141-10] 10.0 ^10.1 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". The Journal of Biological Chemistry. 274 (41): 28950–7. doi:10.1074/jbc.274.41.28950. PMID 10506141.

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