Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEXgene.
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.
The HHEX transcription factor acts as a promoter in some instances and an inhibitor others. 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. HHEX serves to repress VEGFA, another protein which is important in endothelial cell development. 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. HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer. It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism. 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. 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.
^Zamparini, Andrea; Watts, Tim; Gardner, Clare; Tomlinson, Simon; Johnston, Geoffrey; Brickman, Joshua (September 2006). "Hex acts with β-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal". Development133: 3709–3722. doi:10.1242/dev.02516.
^Topcu, Z; Mack D L; Hromas R A; Borden K L (Nov 1999). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene (ENGLAND) 18 (50): 7091–100. doi:10.1038/sj.onc.1203201. ISSN0950-9232. PMID10597310.
Manfioletti G; Gattei V; Buratti E et al. (1995). "Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells". Blood85 (5): 1237–45. PMID7858254.Cite uses deprecated parameter |author-separator= (help)
Topcu Z, Mack DL, Hromas RA, Borden KL (2000). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene18 (50): 7091–100. doi:10.1038/sj.onc.1203201. PMID10597310.
Morgutti M; Demori E; Pecile V et al. (2001). "Genomic organization and chromosome mapping of the human homeobox gene HHEX". Cytogenet. Cell Genet.94 (1–2): 30–2. doi:10.1159/000048778. PMID11701950.Cite uses deprecated parameter |author-separator= (help)
D'Elia AV; Tell G; Russo D et al. (2002). "Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors". J. Clin. Endocrinol. Metab.87 (3): 1376–83. doi:10.1210/jc.87.3.1376. PMID11889211.Cite uses deprecated parameter |author-separator= (help)
Nakagawa T; Abe M; Yamazaki T et al. (2003). "HEX acts as a negative regulator of angiogenesis by modulating the expression of angiogenesis-related gene in endothelial cells in vitro". Arterioscler. Thromb. Vasc. Biol.23 (2): 231–7. doi:10.1161/01.ATV.0000052670.55321.87. PMID12588764.Cite uses deprecated parameter |author-separator= (help)
George A, Morse HC, Justice MJ (2003). "The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells". Oncogene22 (43): 6764–73. doi:10.1038/sj.onc.1206822. PMID14555989.
Minami T; Murakami T; Horiuchi K et al. (2004). "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling". J. Biol. Chem.279 (20): 20626–35. doi:10.1074/jbc.M308730200. PMID15016828.Cite uses deprecated parameter |author-separator= (help)
Puppin C; Presta I; D'Elia AV et al. (2004). "Functional interaction among thyroid-specific transcription factors: Pax8 regulates the activity of Hex promoter". Mol. Cell. Endocrinol.214 (1–2): 117–25. doi:10.1016/j.mce.2003.10.061. PMID15062550.Cite uses deprecated parameter |author-separator= (help)
Swingler TE; Bess KL; Yao J et al. (2004). "The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells". J. Biol. Chem.279 (33): 34938–47. doi:10.1074/jbc.M404488200. PMID15187083.Cite uses deprecated parameter |author-separator= (help)