Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene.[1][2][3]
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.[3]
The HHEX transcription factor acts as a promoter in some instances and an inhibitor others.[4][5] 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.[6] HHEX serves to repress VEGFA, another protein which is important in endothelial cell development.[7] 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.[8] HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer.[9] It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism.[7] 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.[7] 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.[6][7]
Interactions
HHEX has been shown to interact with Promyelocytic leukemia protein.[10]
References
- ^ Bedford FK, Ashworth A, Enver T, Wiedemann LM (May 1993). "HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human". Nucleic Acids Res 21 (5): 1245–9. doi:10.1093/nar/21.5.1245. PMC 309289. PMID 8096636.
- ^ Hromas R, Radich J, Collins S (Oct 1993). "PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells". Biochem Biophys Res Commun 195 (2): 976–83. doi:10.1006/bbrc.1993.2140. PMID 8103988.
- ^ a b "Entrez Gene: HHEX hematopoietically expressed homeobox".
- ^ Denson, Lee; Karpen, Saul; Bogue, Clifford; Jacobs, Harris (August 2000). "Divergent homeobox gene Hex regulates promoter of the Na+-dependent bile acid cotransporter". American Journal of Physiology – Gastrointestinal and Liver Physiology 279 (2): 347–355.
- ^ Brickman, Joshua; Jones, C; Clements, Melanie; Smith, J; Beddington, Rosa (June 2000). "Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function". Development 127: 2303–2315.
- ^ a b Martinez Barbera, Juan; Clements, Melanie; Thomas, Paul; Rodriguez, Tristan; Meloy, Denise; Kioussis, Dimitris; Beddington, Rosa (May 2000). "The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thryoid formation" (PDF). Development 127: 2433–2445.
- ^ a b c d Hallaq, Haifa; Pinter, Emese; Enciso, Josephine; McGrath, James; Zeiss, Caroline; Brueckner, Martina; Madri, Joseph; Jacobs, Harris; Wilson, Christine; Vasavada, Hemaxi; Jiang, Xiaobing; Bogue, Clifford (October 2004). "A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels". Development 131: 5197–5209. doi:10.1242/dev.01393.
- ^ Liao, Wayne; Ho, Chi-Yip; Yi, Lin Yan; Postlewait, John; Stainier, Didier (September 2000). "Hhex and Scl function in parallel to regulate early endothelial and blood differentiation in zebrafish" (PDF). Development 127: 4303–4313.
- ^ 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". Development 133: 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. ISSN 0950-9232. PMID 10597310.
Further reading
- Neidle S, Goodwin GH (1994). "A homology-based molecular model of the proline-rich homeodomain protein Prh, from haematopoietic cells". FEBS Lett. 345 (2–3): 93–8. doi:10.1016/0014-5793(94)00446-3. PMID 7911091.
- Crompton MR; Bartlett TJ; MacGregor AD et al. (1993). "Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells". Nucleic Acids Res. 20 (21): 5661–7. doi:10.1093/nar/20.21.5661. PMC 334400. PMID 1360645.
- Manfioletti G; Gattei V; Buratti E et al. (1995). "Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells". Blood 85 (5): 1237–45. PMID 7858254.
- 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". Oncogene 18 (50): 7091–100. doi:10.1038/sj.onc.1203201. PMID 10597310.
- Pellizzari L; D'Elia A; Rustighi A et al. (2000). "Expression and function of the homeodomain-containing protein Hex in thyroid cells". Nucleic Acids Res. 28 (13): 2503–11. doi:10.1093/nar/28.13.2503. PMC 102703. PMID 10871399.
- Schaefer LK, Wang S, Schaefer TS (2001). "Functional interaction of Jun and homeodomain proteins". J. Biol. Chem. 276 (46): 43074–82. doi:10.1074/jbc.M102552200. PMID 11551904.
- 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. PMID 11701950.
- 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. PMID 11889211.
- Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Topisirovic I; Culjkovic B; Cohen N et al. (2003). "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth". EMBO J. 22 (3): 689–703. doi:10.1093/emboj/cdg069. PMC 140753. PMID 12554669.
- 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. PMID 12588764.
- Puppin C; D'Elia AV; Pellizzari L et al. (2003). "Thyroid-specific transcription factors control Hex promoter activity". Nucleic Acids Res. 31 (7): 1845–52. doi:10.1093/nar/gkg295. PMC 152810. PMID 12655000.
- Bess KL; Swingler TE; Rivett AJ et al. (2003). "The transcriptional repressor protein PRH interacts with the proteasome". Biochem. J. 374 (Pt 3): 667–75. doi:10.1042/BJ20030769. PMC 1223646. PMID 12826010.
- George A, Morse HC, Justice MJ (2003). "The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells". Oncogene 22 (43): 6764–73. doi:10.1038/sj.onc.1206822. PMID 14555989.
- 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. PMID 15016828.
- 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. PMID 15062550.
- 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. PMID 15187083.
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External links
- HHEX protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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