CDX2
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 13: 27.96 – 27.97 Mb | Chr 5: 147.24 – 147.24 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Homeobox protein CDX-2 is a
Function
In common with the two other Cdx genes, CDX2 regulates several essential processes in the development and function of the lower
Later in development, CDX2 is expressed in intestinal epithelial stem cells, which are cells that continuously differentiate into the cells that form the intestinal lining. This differentiation is dependent on CDX2,[10][11] as illustrated by experiments where the expression of this gene was knocked-out or overexpressed in mice. Heterozygous CDX2 knock-outs have intestinal lesions caused by the differentiation of intestinal cells into gastric epithelium; this can be considered a form of homeotic transformation.[12] Conversely, the over-expression of CDX2 leads to the formation of intestinal epithelium in the stomach.[13]
In addition to roles in endoderm, CDX2 is also expressed in very early stages of mouse and human embryonic development, specifically marking the
Pathology
Ectopic expression of CDX2 was reported in more than 85% of the human patients with
Biomarker for intestinal cancer
CDX2 is also used in diagnostic surgical pathology as a marker for gastrointestinal differentiation, especially colorectal.[17]
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.[18] 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.[19] Other genes that have been proposed for this purpose include Hnf4, which is required for gastrulation.[18][20]
Interactions
CDX2 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000165556 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029646 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7698771.
- ^ S2CID 19576530.
- S2CID 4398740.
- S2CID 4252265.
- ^ PMID 15136723.
- PMID 25500896.
- PMID 22190642.
- PMID 10377412.
- PMID 12051735.
- PMID 14718672.
- PMID 17347684.
- PMID 16618413.
- PMID 17906616.
- ^ 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. Archived from the original on May 17, 2008. Retrieved 2008-07-16.
- ^ Saletan W (2004-12-06). "The creepy solution to the stem-cell debate". Slate. Archived from the original on February 14, 2007. Retrieved 2008-07-16.
- S2CID 26102470.
- ^ PMID 10506141.
Further reading
- 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. PMID 7935448.
- Inoue H, Riggs AC, Tanizawa Y, Ueda K, Kuwano A, Liu L, 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. S2CID 46416077.
- 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. S2CID 4252265.
- 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. 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. S2CID 45461007.
- 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. S2CID 45176819.
- 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. 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. 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. 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. 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. 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. 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. S2CID 20514893.
- 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. 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. 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CDX2 genome location and CDX2 gene details page in the UCSC Genome Browser.