Homeobox protein Hox-A5 is a
protein that in humans is encoded by the HOXA5gene.[5][6][7]
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.[7]
HoxA5 is controlled, at least in part, by
DNA methylation.[8] HoxA5 has been shown to upregulate the tumor suppressor p53 and
AKT1 by downregulation of
PTEN.[9] Suppression of HoxA5 has been shown to attenuate
hemangioma growth.[10] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.[11] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of
TNFα-inducible monocyte binding to
HUVECs.[12][13]
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.[14] HoxA5 contains a
C-Amp Response Elements (CRE) in its promoter.[8] POL2 and
CTCF binding are enriched at the
CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.[14]
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.[15][16]HOXA5 has also been nominated as an
oncogene in
glioblastoma. [17]
^Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH (Jul 2011). "Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation". Biochemical and Biophysical Research Communications. 410 (2): 312–6.
doi:
10.1016/j.bbrc.2011.05.139.
PMID21664342.
1hom: DETERMINATION OF THE THREE-DIMENSIONAL STRUCTURE OF THE ANTENNAPEDIA HOMEODOMAIN FROM DROSOPHILA IN SOLUTION BY 1H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
1san: THE DES(1-6)ANTENNAPEDIA HOMEODOMAIN: COMPARISON OF THE NMR SOLUTION STRUCTURE AND THE DNA BINDING AFFINITY WITH THE INTACT ANTENNAPEDIA HOMEODOMAIN