Biology:HOXA5

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.[1][2][3]

Function

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis.[3]

HoxA5 is controlled, at least in part, by DNA methylation.[4] HoxA5 has been shown to upregulate the tumor suppressor p53 and AKT1 by downregulation of PTEN.[5] Suppression of HoxA5 has been shown to attenuate hemangioma growth.[6] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.[7] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFα-inducible monocyte binding to HUVECs.[8][9]

Comparison of the HoxA5 promoter methylation profile across cell types from the least differentiated (human embryonic stem cells) to the most endothelial-like (human umbilical vein endothelial cells, or HUVECs) shows that the HoxA5 promoter is normally heavily methylated in non-differentiated cells and becomes demethylated as cells differentiate down the endothelial lineage.[10] HoxA5 contains a C-Amp Response Elements (CRE) in its promoter.[4] POL2 and CTCF binding are enriched at the CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.[10]

Clinical significance

HoxA5 is suppressed in acute myeloid leukemia (AML), and the DNMT inhibitor decitabine (5Aza) is used to treat this disease. While HoxA5 is known to be hypermethylated in AML, it has not yet been shown whether decitabine directly targets these genes for demethylation.[11][12] HOXA5 has also been nominated as an oncogene in glioblastoma. [13]

See also

References

  1. ↑ "Nomenclature for human homeobox genes". Genomics 7 (3): 460. Jul 1990. doi:10.1016/0888-7543(90)90186-X. PMID 1973146. 
  2. ↑ "Vertebrate homeobox gene nomenclature". Cell 71 (4): 551–3. Nov 1992. doi:10.1016/0092-8674(92)90588-4. PMID 1358459. 
  3. ↑ 3.0 3.1 "Entrez Gene: HOXA5 homeobox A5". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3202. 
  4. ↑ 4.0 4.1 "Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and Atherosclerosis". Arteriosclerosis, Thrombosis, and Vascular Biology 35 (7): 1562–9. Jul 2015. doi:10.1161/ATVBAHA.115.305042. PMID 25953647. 
  5. ↑ "HoxA5 stabilizes adherens junctions via increased Akt1". Cell Adhesion & Migration 1 (4): 185–95. 2007. doi:10.4161/cam.1.4.5448. PMID 19262140. 
  6. ↑ "Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain". Journal of Neuropathology and Experimental Neurology 68 (6): 626–32. Jun 2009. doi:10.1097/NEN.0b013e3181a491ce. PMID 19458547. 
  7. ↑ "Identification of transcriptional targets of HOXA5". The Journal of Biological Chemistry 280 (19): 19373–80. May 2005. doi:10.1074/jbc.M413528200. PMID 15757903. 
  8. ↑ "Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation". Biochemical and Biophysical Research Communications 410 (2): 312–6. Jul 2011. doi:10.1016/j.bbrc.2011.05.139. PMID 21664342. 
  9. ↑ "Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5". Blood 111 (3): 1217–26. Feb 2008. doi:10.1182/blood-2007-07-104133. PMID 17957028. 
  10. ↑ 10.0 10.1 "The role of epigenetics in the endothelial cell shear stress response and atherosclerosis". The International Journal of Biochemistry & Cell Biology 67: 167–76. Oct 2015. doi:10.1016/j.biocel.2015.05.001. PMID 25979369. 
  11. ↑ "HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia". Carcinogenesis 28 (2): 299–309. Feb 2007. doi:10.1093/carcin/bgl133. PMID 16861263. 
  12. ↑ "Level of HOXA5 hypermethylation in acute myeloid leukemia is associated with short-term outcome". The Korean Journal of Laboratory Medicine 30 (5): 469–73. Oct 2010. doi:10.3343/kjlm.2010.30.5.469. PMID 20890077. 
  13. ↑ "Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma". Genes & Development 32 (7–8): 512–523. 2018. doi:10.1101/gad.312157.118. PMID 29632085. 

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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