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DLGAP5  -  discs, large (Drosophila) homolog...

Homo sapiens

Synonyms: DAP-5, DLG1, DLG7, Discs large homolog 7, Disks large-associated protein 5, ...
 
 
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Disease relevance of DLG7

  • DLG7, however, showed restricted expression in testes and cancer, similarly to known germ cell cancer-testis antigens (or germ cell antigens, GCAs) [1].
  • Using the gene expression profiles of Aurora-A as a template to search for and compare transcriptome expression profiles in publicly accessible microarray data sets, we identified HURP (encodes hepatoma upregulated protein) as one of the best Aurora-A-correlated genes [2].
  • Prognostic significance of hepatoma-up-regulated protein expression in patients with urinary bladder transitional cell carcinoma [3].
  • HURP value was correlated with a variety of clinical parameters, including sex, age, tumor grade, stage, multiplicity, tumor shape and recurrence/metastasis during the follow-up period [3].
  • HURP positivity (defined as above 0.1 cut-off value) was detected in 83.6% (92 out of 110) TCC specimens, 4.3% (1 out of 23) of non-TCC urinary cancer and 0% (0 out of 15) of benign urological disease [3].
 

High impact information on DLG7

 

Biological context of DLG7

  • Taken together, these results strongly suggest that HURP is a potential novel cell cycle regulator that may play a role in the carcinogenesis of human cancer cells [6].
  • Immunofluorescence studies revealed that hepatoma up-regulated protein (HURP) localizes to the spindle poles during mitosis [6].
  • Overexpression of HURP in 293T cells resulted in an enhanced cell growth at low serum levels and at polyhema-based, anchorage-independent growth assay [6].
  • We identified 18 antigens encoded by 15 different genes, including DLG7, which is located on chromosome 14q22, a locus previously found to be altered in STS, and the proto-oncogene JUN. Ten of fourteen antigens (71%) do not react with sera from healthy donors, suggesting that antibody recognition takes place during cancer progression [1].
  • Ectopic expression of either the catalytically inactive form of Aurora-A or the HURP-4P mutant, in which the Aurora-A phosphorylation sites were replaced with Ala, resulted in HURP instability and complex disassembly [2].
 

Anatomical context of DLG7

 

Associations of DLG7 with chemical compounds

  • In the SCF(Fbx7) complex, Fbx7 recruits HURP through its C-terminal proline-rich region in a Cdk1-cyclin B-phosphorylation dependent manner [9].
  • We show here that Fbx7, an F-box protein without WD repeats and leucine-rich repeats, is required for the proteasome-mediated proteolysis of the hepatoma up-regulated protein (HURP) [9].
  • Thus, the stability and localization of DLG1 to cell-cell junctions are complex functions determined by the expression and association of particular Stardust family members together with particular LIN7 family members [10].
 

Other interactions of DLG7

  • While this combined approach was simply an initial attempt to answer a range of complex biological questions, our findings do suggest that HURP is a potential oncogenic target of Aurora-A [2].
  • Human hepatoma up-regulated protein (HURP), a cell-cycle regulator, is found consistently overexpressed in human hepatocellular carcinoma [11].
  • Of these uncharacterized proteins, 17 were tagged and localized in transfected mitotic cells, resulting in the identification of six genuine spindle components (KIAA0008, CdcA8, KIAA1187, FLJ12649, FLJ90806, and C20Orf129) [12].
 

Analytical, diagnostic and therapeutic context of DLG7

  • METHODS: Expression levels of KIAA0008 in 27 primary tumors and 23 matched non-tumor liver tissues from HCC patients, and four HCC cell lines with different metastatic potentials were detected by semi-quantitative RT-PCR and real-time RT-PCR [8].
  • We used cryo-electron microscopy and unidirectional surface shadowing to elucidate the structure and conformation of HURP-induced tubulin sheets and their interaction with the inner microtubule [13].

References

  1. Antigens recognized by autologous antibodies of patients with soft tissue sarcoma. Segal, N.H., Blachere, N.E., Shiu, H.Y., Leejee, S., Antonescu, C.R., Lewis, J.J., Wolchok, J.D., Houghton, A.N. Cancer Immun. (2005) [Pubmed]
  2. Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Yu, C.T., Hsu, J.M., Lee, Y.C., Tsou, A.P., Chou, C.K., Huang, C.Y. Mol. Cell. Biol. (2005) [Pubmed]
  3. Prognostic significance of hepatoma-up-regulated protein expression in patients with urinary bladder transitional cell carcinoma. Huang, Y.L., Chiu, A.W., Huan, S.K., Wang, Y.C., Ju, J.P., Lu, C.L. Anticancer Res. (2003) [Pubmed]
  4. HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture. Wong, J., Fang, G. J. Cell Biol. (2006) [Pubmed]
  5. "HURP on" we're off to the kinetochore! Wilde, A. J. Cell Biol. (2006) [Pubmed]
  6. Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma. Tsou, A.P., Yang, C.W., Huang, C.Y., Yu, R.C., Lee, Y.C., Chang, C.W., Chen, B.R., Chung, Y.F., Fann, M.J., Chi, C.W., Chiu, J.H., Chou, C.K. Oncogene (2003) [Pubmed]
  7. HURP is part of a Ran-dependent complex involved in spindle formation. Koffa, M.D., Casanova, C.M., Santarella, R., Köcher, T., Wilm, M., Mattaj, I.W. Curr. Biol. (2006) [Pubmed]
  8. KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma--a functional analysis. Zhao, L., Qin, L.X., Ye, Q.H., Zhu, X.Q., Zhang, H., Wu, X., Chen, J., Liu, Y.K., Tang, Z.Y. J. Cancer Res. Clin. Oncol. (2004) [Pubmed]
  9. Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region. Hsu, J.M., Lee, Y.C., Yu, C.T., Huang, C.Y. J. Biol. Chem. (2004) [Pubmed]
  10. The Stardust Family Protein MPP7 Forms a Tripartite Complex with LIN7 and DLG1 That Regulates the Stability and Localization of DLG1 to Cell Junctions. Bohl, J., Brimer, N., Lyons, C., Vande Pol, S.B. J. Biol. Chem. (2007) [Pubmed]
  11. Using Drosophila eye as a model system to characterize the function of mars gene in cell-cycle regulation. Yang, C.P., Chen, M.S., Liaw, G.J., Chen, S.F., Chou, G., Fan, S.S. Exp. Cell Res. (2005) [Pubmed]
  12. Proteome analysis of the human mitotic spindle. Sauer, G., Körner, R., Hanisch, A., Ries, A., Nigg, E.A., Silljé, H.H. Mol. Cell Proteomics (2005) [Pubmed]
  13. HURP Wraps Microtubule Ends with an Additional Tubulin Sheet That Has a Novel Conformation of Tubulin. Santarella, R.A., Koffa, M.D., Tittmann, P., Gross, H., Hoenger, A. J. Mol. Biol. (2007) [Pubmed]
 
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