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Gene Review

HOXB6  -  homeobox B6

Homo sapiens

Synonyms: HOX2, HOX2B, HU-2, Homeobox protein Hox-2.2, Homeobox protein Hox-2B, ...
 
 
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Disease relevance of HOXB6

 

High impact information on HOXB6

  • Quite unexpectedly, hoxb-5, hoxb-6 transheterozygotes (hoxb-5-hoxb-6+/hoxb-5+ hoxb-6-) also show the third phenotype [5].
  • We have previously reported that certain genes of the HOX2 cluster of homeobox genes on human chromosome 17 are specifically expressed in human leukemic cell lines with erythroid potential, suggesting that these genes are involved in hematopoietic differentiation [6].
  • These data demonstrate that modulation of a specific HOX 2 homeobox gene can change the phenotype of somatic cells and suggest that certain HOX 2 genes play a role in blood cell differentiation [6].
  • The fourth cDNA clone, c13, whose homeo box is approximately 73% homologous to the Hox-2.2 homeo box sequence, is located at chromosome region 2q31----q37 [7].
  • These biologic effects of HOXB6 were largely dependent on DNA binding but independent of direct interaction with PBX1 [8].
 

Biological context of HOXB6

  • Furthermore, endogenous CBP co-precipitates with endogenous HOXB6 in day 14.5 murine fetal liver cells during active globin gene expression in this tissue [1].
  • Abnormalities of the HOXB6 expression may contribute to the development of the leukemic phenotype [2].
  • Taken together, these data suggest that during epidermal development the truncated HOXB6 isoform may function by a mechanism other than as DNA binding protein, and that most of the nuclear, homeodomain-containing HOXB6 protein does not utilize PBX proteins as DNA binding partners in the skin [3].
  • Evolution of the HOXB6 intergenic region: motif conservation at the lateral plate mesoderm (LPM) enhancer element [9].
  • Cytogenetic analysis of a subset of HOXB6-induced AMLs revealed recurrent deletions of chromosome bands 2D-E4, a region frequently deleted in HOXA9-induced AMLs [8].
 

Anatomical context of HOXB6

  • Our data suggest that the homeodomain contains most or all of the important structures required for HOXB6 activity in blood cells [1].
  • HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion [1].
  • The enforced expression of HOXB6 in promyelocytic NB4 cells or in myeloblastic HL60 cells elicited inhibition of the granulocytic or monocytic maturation, respectively [2].
  • In the present study we have analyzed the role of the homeobox gene, HOXB6, in the program of differentiation of the myeloid cell lines, NB4 and HL60 [2].
  • RNA and protein data suggest that a truncated HOXB6 protein, lacking the homeodomain, is expressed in undifferentiated keratinocytes and that the full-length protein is induced by differentiation [3].
 

Associations of HOXB6 with chemical compounds

  • Recently, it has been shown that expression of human HOX 2 genes is sequentially activated by RA beginning from Hox 2.9 at the 3' end of the HOX 2 cluster (A. Simeone, D. Acampora, L. Arcioni, P. W. Andrews, E. Boncinelli, and F. Mavilio, Nature [London] 346:763-766, 1990) [10].
 

Other interactions of HOXB6

  • HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6 [11].
  • Although the HOX homeodomain proteins have been proposed to function as transcription factors, we have demonstrated previously that substantial fractions of the HOXB6 and HOXB4 proteins are localized to the cytoplasm throughout epidermal development [12].
  • This study reports the results of a comparative sequencing study in higher primates, focusing on the intergenic region located between HOXB6 and HOXB7 [9].
  • Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation [5].
  • We also explored structure-function relationships using mutant HOXB6 proteins unable to bind to DNA or a key HOX-binding partner, pre-B-cell leukemia transcription factor-1 (PBX1) [8].
 

Analytical, diagnostic and therapeutic context of HOXB6

  • Using a stepwise screening approach and RT-PCR, we have demonstrated that the human HOXB6, B8, C8 and C9 are overexpressed at various stages of CRC [13].
  • We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis [14].

References

  1. HOXB6 protein is bound to CREB-binding protein and represses globin expression in a DNA binding-dependent, PBX interaction-independent process. Shen, W., Chrobak, D., Krishnan, K., Lawrence, H.J., Largman, C. J. Biol. Chem. (2004) [Pubmed]
  2. Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia. Giampaolo, A., Felli, N., Diverio, D., Morsilli, O., Samoggia, P., Breccia, M., Lo Coco, F., Peschle, C., Testa, U. Leukemia (2002) [Pubmed]
  3. Changes in HOXB6 homeodomain protein structure and localization during human epidermal development and differentiation. Kömüves, L.G., Shen, W.F., Kwong, A., Stelnicki, E., Rozenfeld, S., Oda, Y., Blink, A., Krishnan, K., Lau, B., Mauro, T., Largman, C. Dev. Dyn. (2000) [Pubmed]
  4. Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx-1, in human colon cancer cell lines. Vider, B.Z., Zimber, A., Chastre, E., Gespach, C., Halperin, M., Mashiah, P., Yaniv, A., Gazit, A. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  5. Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Rancourt, D.E., Tsuzuki, T., Capecchi, M.R. Genes Dev. (1995) [Pubmed]
  6. Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines. Shen, W.F., Detmer, K., Mathews, C.H., Hack, F.M., Morgan, D.A., Largman, C., Lawrence, H.J. EMBO J. (1992) [Pubmed]
  7. Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13. Cannizzaro, L.A., Croce, C.M., Griffin, C.A., Simeone, A., Boncinelli, E., Huebner, K. Am. J. Hum. Genet. (1987) [Pubmed]
  8. HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Fischbach, N.A., Rozenfeld, S., Shen, W., Fong, S., Chrobak, D., Ginzinger, D., Kogan, S.C., Radhakrishnan, A., Le Beau, M.M., Largman, C., Lawrence, H.J. Blood (2005) [Pubmed]
  9. Evolution of the HOXB6 intergenic region: motif conservation at the lateral plate mesoderm (LPM) enhancer element. Deinard, A., Dorit, R., Castiglione, C., Jiang, Z., Becker, D., Ruddle, F., Schugart, K., Kidd, K. J. Exp. Zool. (1999) [Pubmed]
  10. Alteration of homeobox gene expression by N-ras transformation of PA-1 human teratocarcinoma cells. Buettner, R., Yim, S.O., Hong, Y.S., Boncinelli, E., Tainsky, M.A. Mol. Cell. Biol. (1991) [Pubmed]
  11. HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema. Golpon, H.A., Geraci, M.W., Moore, M.D., Miller, H.L., Miller, G.J., Tuder, R.M., Voelkel, N.F. Am. J. Pathol. (2001) [Pubmed]
  12. HOXB13 homeodomain protein is cytoplasmic throughout fetal skin development. Kömüves, L.G., Ma, X.K., Stelnicki, E., Rozenfeld, S., Oda, Y., Largman, C. Dev. Dyn. (2003) [Pubmed]
  13. Human colorectal carcinogenesis is associated with deregulation of homeobox gene expression. Vider, B.Z., Zimber, A., Hirsch, D., Estlein, D., Chastre, E., Prevot, S., Gespach, C., Yaniv, A., Gazit, A. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  14. Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system. Giampaolo, A., Acampora, D., Zappavigna, V., Pannese, M., D'Esposito, M., Carè, A., Faiella, A., Stornaiuolo, A., Russo, G., Simeone, A. Differentiation (1989) [Pubmed]
 
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