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Gene Review

USP6  -  ubiquitin specific peptidase 6

Homo sapiens

Synonyms: Deubiquitinating enzyme 6, HRP1, Proto-oncogene TRE-2, TRE17, TRE2, ...
 
 
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Disease relevance of USP6

 

High impact information on USP6

 

Chemical compound and disease context of USP6

 

Biological context of USP6

  • Herein, we characterize four different ABC translocations involving 17p13, and we show that each is associated with a novel USP6 fusion oncogene [10].
  • In summary, these studies show that USP6 oncogenic activation results from heterogeneous genomic mechanisms involving USP6 transcriptional upregulation by juxtaposition with ectopic promoters [10].
  • The oncogenic mechanism in these fusion genes is akin to CDH11-USP6, with the USP6 coding sequences juxtaposed to the promoter regions in each of the four novel translocation partners [10].
  • Point mutations within these motifs significantly reduced the interaction of TRE17 with CaM [11].
  • Our results support previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences play a significant role in the origin of constitutional chromosome aberrations and primate genome evolution [12].
 

Anatomical context of USP6

 

Associations of USP6 with chemical compounds

  • Interestingly, the calcium ionophore A23187 induced accumulation of a polyubiquitinated TRE17 species [11].
  • As two highly conserved amino acids, including the catalytic arginine, are mutated in the oncTre210p TBC domain, we restored these two amino acids and expressed the modified Tre2 cDNA in the yeast mutant [15].
  • Functional asymmetry of the HRP-1 cells was illustrated by the predominant permeation of linoleic acid in the apical-to-basolateral direction across the monolayers [14].
  • Additionally, the HRP-1 cells retain functional activity of angiotensin I converting enzyme and carboxypeptidase N-like enzyme, peptidases characteristic of the trophoblast [14].
  • However, the retinoic acid response of the 716-bp dio1 5' flanking region is unaffected by elimination of TRE2 but is lost with mutations in TRE1 [16].
 

Other interactions of USP6

  • CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter [2].
  • Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity [17].
  • TBC (Tre-2/Bub2/Cdc16) domains are predicted to encode GTPase-activating proteins (GAPs) for Rab family G proteins [18].
  • These results indicate that the 5'-flanking region of the human cystatin A gene confers promoter activity and contains a TRE (TRE-2) that mediates, at least in part, the enhanced expression of this gene by TPA [19].
  • Finally, cell fusion in TGF-beta-treated SM10 and HRP-1 cells was investigated by western blotting analysis of placental alkaline phosphatase and cadherin-11 and by microscopic analyses of cell morphology using green fluorescent protein (GFP) and rhodamine phalloidin staining [20].
 

Analytical, diagnostic and therapeutic context of USP6

  • Both immortalized and malignant cells expressed TRE17 sequences to the same extent, and, according to the restriction site analysis of cloned PCR products, both contained common and rare TRE17 variants in similar proportions [3].
  • The results of this cloning procedure and those of electrophoretic mobility shift assays indicated that the sequence GGGTTAcgtcCGGTCA (nucleotides -716 to -731) represents TRE1 and that the sequence GGGTCC (nucleotides -117 to -112) represents TRE2 [8].
  • Sequence analysis of the gene detected three TPA responsive elements (TRE-1, TRE-2, and TRE-3) and one AP-2 site on the 5' upstream promoter region [19].
  • 1. In complementation tests, mutants HRP-1, DS28-6, and V.24.1 all appeared to be in the same complementation group [21].
  • The assistive system comprised the novel controller, the power and output stages of an eight-channel FES system (IEEE Trans Rehabil Eng, TRE-2 (1994) 234), ankle-foot orthoses, and a rolling walker [22].

References

  1. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Oliveira, A.M., Perez-Atayde, A.R., Inwards, C.Y., Medeiros, F., Derr, V., Hsi, B.L., Gebhardt, M.C., Rosenberg, A.E., Fletcher, J.A. Am. J. Pathol. (2004) [Pubmed]
  2. USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Oliveira, A.M., Hsi, B.L., Weremowicz, S., Rosenberg, A.E., Dal Cin, P., Joseph, N., Bridge, J.A., Perez-Atayde, A.R., Fletcher, J.A. Cancer Res. (2004) [Pubmed]
  3. Identification of novel sequences in the repertoire of hypervariable TRE17 genes from immortalized nonmalignant and malignant human keratinocytes. Onno, M., Nakamura, T., Hillova, J., Hill, M. Gene (1993) [Pubmed]
  4. A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat. Marriott, S.J., Lindholm, P.F., Brown, K.M., Gitlin, S.D., Duvall, J.F., Radonovich, M.F., Brady, J.N. Mol. Cell. Biol. (1990) [Pubmed]
  5. Heterogeneous transforming growth factor (TGF)-beta unresponsiveness and loss of TGF-beta receptor type II expression caused by histone deacetylation in lung cancer cell lines. Osada, H., Tatematsu, Y., Masuda, A., Saito, T., Sugiyama, M., Yanagisawa, K., Takahashi, T. Cancer Res. (2001) [Pubmed]
  6. Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1. Pérez-Cañadillas, J.M. EMBO J. (2006) [Pubmed]
  7. The Tre2 (USP6) oncogene is a hominoid-specific gene. Paulding, C.A., Ruvolo, M., Haber, D.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Identification of thyroid hormone response elements in the human fatty acid synthase promoter. Xiong, S., Chirala, S.S., Hsu, M.H., Wakil, S.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Decreased ratio of total progesterone to total estradiol receptor levels in endometria of women with adult dysfunctional uterine bleeding. Gorodeski, I.G., Geier, A., Siegal, A., Beery, R., Lunenfeld, B., Langzam, J., Bahari, C.M. Gynecol. Obstet. Invest. (1986) [Pubmed]
  10. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oliveira, A.M., Perez-Atayde, A.R., Dal Cin, P., Gebhardt, M.C., Chen, C.J., Neff, J.R., Demetri, G.D., Rosenberg, A.E., Bridge, J.A., Fletcher, J.A. Oncogene (2005) [Pubmed]
  11. Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6. Shen, C., Ye, Y., Robertson, S.E., Lau, A.W., Mak, D.O., Chou, M.M. J. Biol. Chem. (2005) [Pubmed]
  12. Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations. Ou, Z., Jarmuz, M., Sparagana, S.P., Michaud, J., Décarie, J.C., Yatsenko, S.A., Nowakowska, B., Furman, P., Shaw, C.A., Shaffer, L.G., Lupski, J.R., Chinault, A.C., Cheung, S.W., Stankiewicz, P. Hum. Genet. (2006) [Pubmed]
  13. The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. Masuda-Robens, J.M., Kutney, S.N., Qi, H., Chou, M.M. Mol. Cell. Biol. (2003) [Pubmed]
  14. Permeability and metabolic properties of a trophoblast cell line (HRP-1) derived from normal rat placenta. Shi, F., Soares, M.J., Avery, M., Liu, F., Zhang, X., Audus, K.L. Exp. Cell Res. (1997) [Pubmed]
  15. Expression in a RabGAP yeast mutant of two human homologues, one of which is an oncogene. Bizimungu, C., De Neve, N., Burny, A., Bach, S., Bontemps, F., Portetelle, D., Vandenbol, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Further characterization of thyroid hormone response elements in the human type 1 iodothyronine deiodinase gene. Zhang, C.Y., Kim, S., Harney, J.W., Larsen, P.R. Endocrinology (1998) [Pubmed]
  17. Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity. Itoh, T., Satoh, M., Kanno, E., Fukuda, M. Genes Cells (2006) [Pubmed]
  18. The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6. Martinu, L., Masuda-Robens, J.M., Robertson, S.E., Santy, L.C., Casanova, J.E., Chou, M.M. Mol. Cell. Biol. (2004) [Pubmed]
  19. Structure and transcriptional regulation of the human cystatin A gene. The 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (-272 to -278) on cystatin A gene is critical for TPA-dependent regulation. Takahashi, H., Asano, K., Kinouchi, M., Ishida-Yamamoto, A., Wuepper, K.D., Iizuka, H. J. Biol. Chem. (1998) [Pubmed]
  20. Transforming growth factor-beta induces differentiation of the labyrinthine trophoblast stem cell line SM10. Selesniemi, K., Reedy, M., Gultice, A., Guilbert, L.J., Brown, T.L. Stem Cells Dev. (2005) [Pubmed]
  21. Novel method for isolating mammalian cells defective in fluid-phase endocytosis. Wang, R.H., Colbaugh, P.A., Kuo, P., Bau, M.Y., Poppe, L.M., Draper, R.K. Somat. Cell Mol. Genet. (1992) [Pubmed]
  22. New controller for functional electrical stimulation systems. Fisekovic, N., Popovic, D.B. Medical engineering & physics. (2001) [Pubmed]
 
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