Homeobox protein CDX-1 is a protein in humans that is encoded by the CDX1gene.[1][2] CDX1 is expressed in the developing endoderm and its expression persists in the intestine throughout adulthood.[3] CDX1 protein expression varies along the intestine, with high expression in intestinal crypts and diminishing expression along intestinal villi.[4]
This gene is a member of the caudal-related homeoboxtranscription factor family. The encoded DNA-binding protein regulates intestine-specific gene expression and enterocyte differentiation. It has been shown to induce expression of the intestinal alkaline phosphatase gene, and inhibit beta-catenin/T-cell factor transcriptional activity.[2]
CDX1 has also been shown to play an important role in embryonic epicardial development. It has been demonstrated that CDX proteins suppress cardiac differentiation in both zebrafish and mouse embryonic stem cells, but the overall mechanism for how this happens is poorly understood.[5] However, CDX1 has been shown to be transiently expressed in the embryonic heart 11.5 days post coitum (dpc). This transient expression is thought to induce epicardial epithelial-to-mesynchemal transition and thus proper cardiovascular formation. It has been shown that low-dose CDX1 induction caused enhanced migration and differentiation of epicardium-derived cells into vascular smooth muscle, where as continued high dose induction of CDX1 or CDX1 deficiency diminished the ability of these cells to migrate and differentiate into smooth muscle by the actions of TGF-β1. Furthermore, CDX1 induction also altered transcript expression of genes related to cell adhesions for EMT and angiogenesis.[6] Therefore, along with its known roles in intestinal patterning and differentiation, CDX1 is also shown to be important in epicardial development.
References
↑Bonner CA, Loftus SK, Wasmuth JJ (July 1995). "Isolation, characterization, and precise physical localization of human CDX1, a caudal-type homeobox gene". Genomics. 28 (2): 206–11. doi:10.1006/geno.1995.1132. PMID8530027.
↑Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (October 2007). "Identification of stem cells in small intestine and colon by marker gene Lgr5". Nature. 449 (7165): 1003–7. doi:10.1038/nature06196. PMID17934449.
"Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. The Treacher Collins Syndrome Collaborative Group". Nature Genetics. 12 (2): 130–6. February 1996. doi:10.1038/ng0296-130. PMID8563749.
Mallo GV, Rechreche H, Frigerio JM, Rocha D, Zweibaum A, Lacasa M, Jordan BR, Dusetti NJ, Dagorn JC, Iovanna JL (February 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. PMID9036867.
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. PMID11846061.
Suh ER, Ha CS, Rankin EB, Toyota M, Traber PG (September 2002). "DNA methylation down-regulates CDX1 gene expression in colorectal cancer cell lines". The Journal of Biological Chemistry. 277 (39): 35795–800. doi:10.1074/jbc.M205567200. PMID12124393.
Domon-Dell C, Schneider A, Moucadel V, Guerin E, Guenot D, Aguillon S, Duluc I, Martin E, Iovanna J, Launay JF, Duclos B, Chenard MP, Meyer C, Oudet P, Kedinger M, Gaub MP, Freund JN (September 2003). "Cdx1 homeobox gene during human colon cancer progression". Oncogene. 22 (39): 7913–21. doi:10.1038/sj.onc.1206756. PMID12970739.
Rankin EB, Xu W, Silberg DG, Suh E (May 2004). "Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine". American Journal of Physiology. Gastrointestinal and Liver Physiology. 286 (5): G872–80. doi:10.1152/ajpgi.00326.2003. PMID14715525.
Guo RJ, Huang E, Ezaki T, Patel N, Sinclair K, Wu J, Klein P, Suh ER, Lynch JP (August 2004). "Cdx1 inhibits human colon cancer cell proliferation by reducing beta-catenin/T-cell factor transcriptional activity". The Journal of Biological Chemistry. 279 (35): 36865–75. doi:10.1074/jbc.M405213200. PMID15215241.
Alkhoury F, Malo MS, Mozumder M, Mostafa G, Hodin RA (August 2005). "Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2". American Journal of Physiology. Gastrointestinal and Liver Physiology. 289 (2): G285–90. doi:10.1152/ajpgi.00037.2005. PMID15774940.
