Homeobox protein CDX-2

CDX2
Identifiers
Aliases	CDX2, CDX-3, CDX2/AS, CDX3, caudal type homeobox 2, Cdx2
External IDs	OMIM: 600297; MGI: 88361; HomoloGene: 968; GeneCards: CDX2; OMA:CDX2 - orthologs
Gene location (Human)
Chr.	Chromosome 13 (human)
End	27,969,315 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	147,244,080 bp
RNA expression pattern
	Top expressed in
	mucosa of transverse colon; ; rectum; ; duodenum; ; epithelium of colon; ; mucosa of ileum; ; mucosa of sigmoid colon; ; appendix; ; jejunal mucosa; ; body of pancreas; ; islet of Langerhans;
	Top expressed in
	Paneth cell; ; tail of embryo; ; crypt of lieberkuhn of small intestine; ; primitive streak; ; migratory enteric neural crest cell; ; ileum; ; jejunum; ; duodenum; ; Epithelium of large intestine; ; left colon;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	RNA polymerase II cis-regulatory region sequence-specific DNA binding; DNA binding; sequence-specific DNA binding; transcription corepressor activity; DNA-binding transcription factor activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; double-stranded DNA binding; DNA-binding transcription factor activity, RNA polymerase II-specific; methyl-CpG binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding;
Cellular component	transcription repressor complex; nucleoplasm; condensed nuclear chromosome; nucleus; protein-containing complex;
Biological process	pattern specification process; cell differentiation; regulation of transcription, DNA-templated; regulation of somitogenesis; somatic stem cell population maintenance; endosome to lysosome transport; placenta development; regulation of transcription by RNA polymerase II; labyrinthine layer development; negative regulation of transcription by RNA polymerase II; transcription by RNA polymerase II; transcription, DNA-templated; positive regulation of transcription, DNA-templated; multicellular organism development; blood vessel development; trophectodermal cell differentiation; establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of cell differentiation; intestinal epithelial cell differentiation; positive regulation of cell population proliferation; animal organ morphogenesis; anterior/posterior axis specification; blastocyst development; anterior/posterior pattern specification;
	Sources:Amigo / QuickGO
Orthologs
	1045
	12591
	ENSG00000165556
	ENSMUSG00000029646
	Q99626
	P43241
	NM_001265; NM_001354700
	NM_007673
	NP_001256; NP_001341629
	NP_031699
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5]

Function

Cdx2 is the gene that directs early embryogenesis in mice. It is required to form the placenta.^[6]

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.^[7]^[7]^[8] CDX2 is also implicated in the pathogenesis of Barrett's esophagus where 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.^[9]

Biomarker for intestinal cancer

CDX2 is also used in diagnostic surgical pathology as a marker for gastrointestinal differentiation, especially colorectal.^[10]

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.^[11] 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.^[12] Other genes that have been proposed for this purpose include Hnf4, which is required for gastrulation.^[11]^[13]

Interactions

CDX2 has been shown to interact with EP300,^[14] and PAX6.^[14]

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.
^ 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.
^ ^a ^b 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.
^ ^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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ 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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ 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.
^ ^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". The Journal of Biological Chemistry. 274 (41): 28950–7. doi:10.1074/jbc.274.41.28950. PMID 10506141.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

CDX2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165556 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029646 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7698771-5] 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.

[pmid15136723-6] 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_2004-7] 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_2007-8] 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_2006-9] 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.

[pmid17906616-10] 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-11] 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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[Slate_url-12] 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. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[pmid17402791-13] 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.

[pmid10506141-14] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]