Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEXgene and also known as Proline Rich Homeodomain protein PRH.[5][6][7]
This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation but the expression of this protein is not limited to hematopoietic cells.[7]
The HHEX transcription factor acts as a activator of transcription in some instances and a repressor of transcription others.[8][9] It interacts with a number of other signaling molecules to play an important role in the development of multiple organs, such as the liver, thyroid and forebrain.[10] HHEX serves to repress VEGFA, another protein which is important in endothelial cell development.[11] SCL, a significant transcription factor for blood and endothelial cell differentiation, is shown to interact with HHEX to promote the correct development of the hematopoiesis process.[12] HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer.[13] It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism.[11] The importance of this transcription factor is illustrated by the inability of HHEX knockout mice embryos to survive gestation. Without the expression of HHEX, these mice embryos die in utero between Day 13 and Day 16.[11] HHEX knockout mice display a range of abnormalities including forebrain abnormalities in various levels of severity, as well as a number of other defects including heart, vasculature, liver, monocyte, and thyroid abnormalities.[10][11] The HHEX protein is important in a variety of cancers and it can act as an tumour suppressor protein or as an oncoprotein depending on the cancer type.
^Hromas R, Radich J, Collins S (Sep 1993). "PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells". Biochemical and Biophysical Research Communications. 195 (2): 976–83. doi:10.1006/bbrc.1993.2140. PMID8103988.
^Liao W, Ho CY, Yan YL, Postlethwait J, Stainier DY (Oct 2000). "Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish". Development. 127 (20): 4303–13. doi:10.1242/dev.127.20.4303. PMID11003831.
Manfioletti G, Gattei V, Buratti E, Rustighi A, De Iuliis A, Aldinucci D, Goodwin GH, Pinto A (Mar 1995). "Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells". Blood. 85 (5): 1237–45. doi:10.1182/blood.V85.5.1237.bloodjournal8551237. PMID7858254.
Morgutti M, Demori E, Pecile V, Amoroso A, Rustighi A, Manfioletti G (2001). "Genomic organization and chromosome mapping of the human homeobox gene HHEX". Cytogenetics and Cell Genetics. 94 (1–2): 30–2. doi:10.1159/000048778. PMID11701950. S2CID28072668.
