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HOXB2  -  homeobox B2

Homo sapiens

Synonyms: HOX2, HOX2H, Homeobox protein Hox-2.8, Homeobox protein Hox-2H, Homeobox protein Hox-B2, ...
 
 
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Disease relevance of HOXB2

  • CONCLUSIONS: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions [1].
  • As for the hoxb-1 mutations, the facial paralysis observed in mice homozygous for the hoxb-2 mutation results from a failure to form the somatic motor component of the VIIth (facial) nerve which controls the muscles of facial expression [2].
  • The expression of both genes was also examined in the brain cancer cell lines U-251 MG, D54 and SH-SY5Y and the invasive capacity of glioblastoma cells U-251 MG overexpressing hK7 or hK8 was also investigated in an in vitro Matrigel assay [3].
  • Overexpression of hK7 protein by cultivated brain tumor cells significantly enhanced the invasive potential in the Matrigel invasion assay, in contrast to cells overexpressing hK8 protein [3].
  • Human kallikrein 8 (hK8), whose gene was originally cloned as the human ortholog of a mouse brain protease, is known to be associated with diseases such as ovarian cancer and Alzheimer's disease [4].
 

High impact information on HOXB2

  • Because no other relationship had been established between the 87-kD K562 protein and the HOXB2 protein other than their ability to bind ot the same DNA sequences, we have investigated whether the two proteins are related antigenically [5].
  • A lambda gt11 K562 cDNA clone encoding a portion of the HOXB2 (formerly HOX2H) homeobox gene was isolated on the basis of the ability of its beta-galactosidase fusion protein to bind to the same DNA sequences as the 87-kD K562 protein [5].
  • We now report on the expression patterns of the entire HOX 2 cluster, consisting of nine homeobox genes, in a broad survey of leukemic cell lines of different phenotypes [6].
  • These data show that in human hematopoietic cell lines HOX 2 homeobox gene expression is largely restricted to cells of erythroid phenotype and suggest that these genes play a role in erythropoiesis [6].
  • Within erythroid cell lines, many of the HOX 2 genes are expressed as multiple transcripts [6].
 

Chemical compound and disease context of HOXB2

 

Biological context of HOXB2

 

Anatomical context of HOXB2

  • HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas [1].
  • These findings suggest a regulatory hierarchy in which GATA-1 is upstream of the HOXB2 gene in erythroid cells [8].
  • 3) Studies with antisense oligomer targeting HOXB2 mRNA suggest an important role for 82 in NK cell proliferation, possibly in part via the IL-2R [10].
  • A putative 30-kDa protein was detected in the tissue extracts from adult rat epididymis and caudal spermatozoa, and a 37-kDa protein was detected in the rat embryo when probed with a polyclonal antibody against HOXB2 protein [11].
  • We have now identified a PLZF binding site (PLZF-RE) in an enhancer region of Hoxb2 that itself is required for directing high-level expression in rhombomers 3 and 5 of the developing hindbrain [12].
 

Associations of HOXB2 with chemical compounds

  • METHODS: Various concentrations of HOXB2 asodn modified by thiophosphate transfected the induction of liposome into HUVECs [13].
  • 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) [14].
  • Using stable CACO-2 transfectants expressing keratin 8 (K8) antisense RNA under a tetracycline-responsive element, we showed that the actin-ezrin scaffold cannot assemble in the absence of intermediate filaments (IFs) [15].
  • All synthetic substrates tested containing either arginine or lysine at P1 position were cleaved by hK8 [4].
  • The activity of hK8 was inhibited by antipain, chymostatin, and leupeptin [4].
 

Physical interactions of HOXB2

 

Other interactions of HOXB2

  • 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 [16].
  • Since some genes (HOXB2, HOXB4, HOXB7) were always inactive when unmethylated, this unexpected relationship might indicate their key function(s) in the HOX gene network [17].
  • The sternal defects seen in hoxb-2 mutant mice are similar to those previously reported for hoxb-4 mutant mice (Ramirez-Solis, R., Zheng, H., Whiting, J., Krumlauf, R. and Bradley. A. (1993) Cell 73, 279-294) [2].
  • Consistent with this proposal, we found that the hoxb-2 mutation disrupts the expression of hoxb-1 in cis [2].
  • Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was found only in tumor tissues [18].
 

Analytical, diagnostic and therapeutic context of HOXB2

  • Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens [1].
  • The present work showed that antisera directed against either SATB1 or HOXB2 reacted specifically with the entire gammaPE complex in electrophoretic mobility shift assays (EMSAs), suggesting that the two proteins can bind to the gammaPE binding site simultaneously [9].
  • MTT a nd RT-PCR methods were employed to determine the effect of different conc ent rations of asodn on the endothelial proliferation and the expression level of HOXB2 mRNA [13].
  • Mice with a disruption in the hoxb-2 locus were generated by gene targeting [2].
  • We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis [19].

References

  1. Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia. Segara, D., Biankin, A.V., Kench, J.G., Langusch, C.C., Dawson, A.C., Skalicky, D.A., Gotley, D.C., Coleman, M.J., Sutherland, R.L., Henshall, S.M. Clin. Cancer Res. (2005) [Pubmed]
  2. Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4. Barrow, J.R., Capecchi, M.R. Development (1996) [Pubmed]
  3. The role of human tissue kallikreins 7 and 8 in intracranial malignancies. Prezas, P., Scorilas, A., Yfanti, C., Viktorov, P., Agnanti, N., Diamandis, E., Talieri, M. Biol. Chem. (2006) [Pubmed]
  4. Activation and enzymatic characterization of recombinant human kallikrein 8. Kishi, T., Cloutier, S.M., Kündig, C., Deperthes, D., Diamandis, E.P. Biol. Chem. (2006) [Pubmed]
  5. The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus. Sengupta, P.K., Lavelle, D.E., DeSimone, J. Blood (1994) [Pubmed]
  6. Erythroid-restricted expression of homeobox genes of the human HOX 2 locus. Mathews, C.H., Detmer, K., Boncinelli, E., Lawrence, H.J., Largman, C. Blood (1991) [Pubmed]
  7. Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and the upstream sequence of the Otx2 gene in embryonal carcinoma cells. Guazzi, S., Pintonello, M.L., Viganò, A., Boncinelli, E. J. Biol. Chem. (1998) [Pubmed]
  8. Transcription factor GATA-1 regulates human HOXB2 gene expression in erythroid cells. Vieille-Grosjean, I., Huber, P. J. Biol. Chem. (1995) [Pubmed]
  9. The gammaPE complex contains both SATB1 and HOXB2 and has positive and negative roles in human gamma-globin gene regulation. Case, S.S., Huber, P., Lloyd, J.A. DNA Cell Biol. (1999) [Pubmed]
  10. HOXB cluster genes in activated natural killer lymphocytes: expression from 3'-->5' cluster side and proliferative function. Quaranta, M.T., Petrini, M., Tritarelli, E., Samoggia, P., Carè, A., Bottero, L., Testa, U., Peschle, C. J. Immunol. (1996) [Pubmed]
  11. HOXBES2: A Novel Epididymal HOXB2 Homeoprotein and Its Domain-Specific Association with Spermatozoa. Prabagaran, E., Bandivdekar, A.H., Dighe, V., Raghavan, V.P. Biol. Reprod. (2007) [Pubmed]
  12. Regulation of Hoxb2 by APL-associated PLZF protein. Ivins, S., Pemberton, K., Guidez, F., Howell, L., Krumlauf, R., Zelent, A. Oncogene (2003) [Pubmed]
  13. Effect of anti-sense oligodeoxynucleotides homeobox B2 on the proliferation and expression of primary human umbilical vein endothelial cells. Liu, X., Zhang, X. Chinese journal of traumatology = Zhonghua chuang shang za zhi / Chinese Medical Association. (2002) [Pubmed]
  14. 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]
  15. Intermediate filaments interact with dormant ezrin in intestinal epithelial cells. Wald, F.A., Oriolo, A.S., Casanova, M.L., Salas, P.J. Mol. Biol. Cell (2005) [Pubmed]
  16. 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]
  17. Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers. Flagiello, D., Poupon, M.F., Cillo, C., Dutrillaux, B., Malfoy, B. FEBS Lett. (1996) [Pubmed]
  18. HOXB homeobox gene expression in cervical carcinoma. López, R., Garrido, E., Piña, P., Hidalgo, A., Lazos, M., Ochoa, R., Salcedo, M. Int. J. Gynecol. Cancer (2006) [Pubmed]
  19. 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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