Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: HHEX - hematopoietically expressed homeobox

Homo sapiens

Synonyms: Hematopoietically expressed homeobox, Hematopoietically-expressed homeobox, HEX, HMPH, homeobox, hematopoietically expressed, Homeobox protein HEX, Homeobox protein PRH, HOX11L-PEN, PRH, PRHX

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Swingler, T.E., Hromas, R., Kondo, K., Soufi, A., Wain, E.M., et al.

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High impact information on HHEX

Through this interaction, PRH inhibits eIF4E-dependent mRNA transport and subsequent transformation [1].
Two candidate enhancers discovered in this way were located in intron 1 of the Fli-1 and PRH/Hex genes, both transcription factors previously implicated in controlling blood and endothelial development [2].
Here we demonstrate that the proline-rich N-terminal domain of PRH binds to TLE1 in vitro and in yeast two-hybrid assays [3].
Finally, we show that a mutation in the PRH N-terminal domain that blocks the PRH-TLE1 interaction in vitro eliminates co-repression [3].
The proline-rich homeodomain protein (PRH/Hex) is important in the control of cell proliferation and differentiation and in the regulation of multiple processes in embryonic development [3].

Biological context of HHEX

Genomic organization and chromosome mapping of the human homeobox gene HHEX [4].
We discuss these results in terms of the roles of PRH and TLE in cell differentiation and development [3].
The PRH homeodomain represses transcription by binding to TATA box sequences, whereas the proline-rich N-terminal domain of PRH can repress transcription when attached to a heterologous DNA-binding domain [3].
Within the first region of deletion at 10q23.33-10q24.1, around microsatellite marker D10S185 (2.77 Mb), 23 genes were identified, including three (KIF11, HHEX, and HELLS) with functions that, if dysregulated, could be critical in MF and SS [5].
We discuss these findings in terms of the biological role of PRH in gene regulation and the control of cell proliferation [6].

Anatomical context of HHEX

Using yeast two-hybrid screening, we identified hematopoietically expressed homeobox (Hex) as a GATA-binding partner in endothelial cells [7].
Northern blot hybridization indicates that PRH is preferentially expressed in myeloid and liver cells [8].
Using degenerate oligonucleotide primers corresponding to conserved homeobox sequences in the polymerase chain reaction (PCR), we cloned from the HL60 promyelocytic cell line a homeobox gene we now designate PRH [8].
Homeobox protein Hex facilitates serum responsive factor-mediated activation of the SM22alpha gene transcription in embryonic fibroblasts [9].

Associations of HHEX with chemical compounds

We also directly analysed HMPH, an active free hydrazine form of genotoxic agaritine, and obtained direct evidence of its absence from mushrooms [10].
A new method with good sensitivity and specificity for detecting and quantifying genotoxic hydrazines, agaritine and 4-(hydroxymethyl)phenylhydrazine (HMPH), was developed using liquid chromatography-electrospray tandem mass spectrometry (MS) [10].

Other interactions of HHEX

In the present study, we report the genomic reconstruction of the human homeobox-containing gene HHEX by the use of the data available in public databases [4].

Analytical, diagnostic and therapeutic context of HHEX

We show that PRH and TLE proteins are co-expressed in hematopoietic cells and interact in co-immunoprecipitation assays [3].
PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells [8].
Here, we show using a variety of techniques including gel-filtration, analytical ultracentrifugation, electron microscopy and in vitro cross-linking, that purified recombinant PRH is oligomeric and we use in vivo cross-linking to confirm that this protein exists as oligomers in cells [11].
The majority of cases of per rectal haemorrhage (PRH) are due to colorectal causes within the diagnostic reach of the colonoscope [12].

References

The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. Topisirovic, I., Culjkovic, B., Cohen, N., Perez, J.M., Skrabanek, L., Borden, K.L. EMBO J. (2003)
Genome-wide identification of cis-regulatory sequences controlling blood and endothelial development. Donaldson, I.J., Chapman, M., Kinston, S., Landry, J.R., Knezevic, K., Piltz, S., Buckley, N., Green, A.R., Göttgens, B. Hum. Mol. Genet. (2005)
The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells. Swingler, T.E., Bess, K.L., Yao, J., Stifani, S., Jayaraman, P.S. J. Biol. Chem. (2004)
Genomic organization and chromosome mapping of the human homeobox gene HHEX. Morgutti, M., Demori, E., Pecile, V., Amoroso, A., Rustighi, A., Manfioletti, G. Cytogenet. Cell Genet. (2001)
Fine mapping of chromosome 10q deletions in mycosis fungoides and sezary syndrome: identification of two discrete regions of deletion at 10q23.33-24.1 and 10q24.33-25.1. Wain, E.M., Mitchell, T.J., Russell-Jones, R., Whittaker, S.J. Genes Chromosomes Cancer (2005)
The transcriptional repressor protein PRH interacts with the proteasome. Bess, K.L., Swingler, T.E., Rivett, A.J., Gaston, K., Jayaraman, P.S. Biochem. J. (2003)
Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling. Minami, T., Murakami, T., Horiuchi, K., Miura, M., Noguchi, T., Miyazaki, J., Hamakubo, T., Aird, W.C., Kodama, T. J. Biol. Chem. (2004)
PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells. Hromas, R., Radich, J., Collins, S. Biochem. Biophys. Res. Commun. (1993)
Homeobox protein Hex facilitates serum responsive factor-mediated activation of the SM22alpha gene transcription in embryonic fibroblasts. Oyama, Y., Kawai-Kowase, K., Sekiguchi, K., Sato, M., Sato, H., Yamazaki, M., Ohyama, Y., Aihara, Y., Iso, T., Okamaoto, E., Nagai, R., Kurabayashi, M. Arterioscler. Thromb. Vasc. Biol. (2004)
Determination of genotoxic phenylhydrazine agaritine in mushrooms using liquid chromatography-electrospray ionization tandem mass spectrometry. Kondo, K., Watanabe, A., Iwanaga, Y., Abe, I., Tanaka, H., Nagaoka, M.H., Akiyama, H., Maitani, T. Food additives and contaminants. (2006)
Oligomerisation of the Developmental Regulator Proline Rich Homeodomain (PRH/Hex) is Mediated by a Novel Proline-rich Dimerisation Domain. Soufi, A., Smith, C., Clarke, A.R., Gaston, K., Jayaraman, P.S. J. Mol. Biol. (2006)
Small bowel causes of per rectum haemorrhage. Klinvimol, T., Ho, Y.H., Parry, B.R., Goh, H.S. Ann. Acad. Med. Singap. (1994)