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Gene Review

DPH1  -  diphthamide biosynthesis 1

Homo sapiens

Synonyms: DPH-like 1, DPH1 homolog, DPH2-like 1, DPH2L, DPH2L1, ...
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Disease relevance of DPH1


High impact information on DPH1


Chemical compound and disease context of DPH1


Biological context of DPH1


Anatomical context of DPH1


Associations of DPH1 with chemical compounds

  • Our results are in contrast to a previous report and show that OVCA2, not OVCA1 mRNA and protein, is downregulated in response to RA and 4HPR [18].
  • Previous work has shown that OVCA 433 cells are growth inhibited by glucocorticoids and contain 14,000 glucocorticoid receptors per cell with an affinity for dexamethasone (Kd = 6.6 x 10(-9) M) which corresponds well with the concentration required for half-maximal CA125 inhibition [19].
  • One OCa cell line, OVCA 433, was found to be nonresponsive to androgen stimulation [20].
  • Here we show that release of CA125 by OVCA 433 cells is 90 to 95% inhibited by treatment with 1 x 10(-7) M dexamethasone, as determined using a biotin-based enzyme-linked immunosorbent assay utilizing OC125 monoclonal antibodies to CA125 [19].
  • Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor 2 [21].

Other interactions of DPH1

  • Using allelic loss mapping and positional cloning methods, we have recently identified two novel genes, which we refer to as OVCA1 and OVCA2, that map to 17p13 [22].
  • Candidate genes within this region are HIC-1, a potential tumour-suppressor gene, and DPH2L, a gene that has been cloned from the ovarian critical region [23].
  • We have identified a cDNA corresponding to the sequence of the known gene diphthamide biosynthesis protein 2-like (DPH2L) [24].

Analytical, diagnostic and therapeutic context of DPH1


  1. Expression of OVCA1, a candidate tumor suppressor, is reduced in tumors and inhibits growth of ovarian cancer cells. Bruening, W., Prowse, A.H., Schultz, D.C., Holgado-Madruga, M., Wong, A., Godwin, A.K. Cancer Res. (1999) [Pubmed]
  2. Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis. Chen, C.M., Behringer, R.R. Genes Dev. (2004) [Pubmed]
  3. A plasma membrane-associated component of ovarian adenocarcinoma cells enhances the catalytic efficiency of matrix metalloproteinase-2. Young, T.N., Pizzo, S.V., Stack, M.S. J. Biol. Chem. (1995) [Pubmed]
  4. Alkylating agents and immunotoxins exert synergistic cytotoxic activity against ovarian cancer cells. Mechanism of action. Lidor, Y.J., O'Briant, K.C., Xu, F.J., Hamilton, T.C., Ozols, R.F., Bast, R.C. J. Clin. Invest. (1993) [Pubmed]
  5. OVCA1: tumor suppressor gene. Chen, C.M., Behringer, R.R. Curr. Opin. Genet. Dev. (2005) [Pubmed]
  6. Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Liu, S., Milne, G.T., Kuremsky, J.G., Fink, G.R., Leppla, S.H. Mol. Cell. Biol. (2004) [Pubmed]
  7. Endothelin-1 induces tumor proteinase activation and invasiveness of ovarian carcinoma cells. Rosanò, L., Varmi, M., Salani, D., Di Castro, V., Spinella, F., Natali, P.G., Bagnato, A. Cancer Res. (2001) [Pubmed]
  8. Different mechanisms contribute to simultaneous inhibition of urokinase and tissue-type plasminogen activators by glucocorticoids in human ovarian carcinoma cells. Karlan, B.Y., Rivero, J.A., Crabtree, M.E., Littlefield, B.A. Mol. Endocrinol. (1989) [Pubmed]
  9. Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Scambia, G., Ranelletti, F.O., Panici, P.B., Piantelli, M., Bonanno, G., De Vincenzo, R., Ferrandina, G., Rumi, C., Larocca, L.M., Mancuso, S. Br. J. Cancer (1990) [Pubmed]
  10. Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Scambia, G., De Vincenzo, R., Ranelletti, F.O., Panici, P.B., Ferrandina, G., D'Agostino, G., Fattorossi, A., Bombardelli, E., Mancuso, S. Eur. J. Cancer (1996) [Pubmed]
  11. Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells. Ferrandina, G., Scambia, G., Benedetti Panici, P., Bonanno, G., De Vincenzo, R., Rumi, C., Bussa, S., Genuardi, M., Spica Romano, V., Mancuso, S. Mol. Cell. Endocrinol. (1992) [Pubmed]
  12. Steroid hormonal independence of HER-2/neu mRNA expression in four human ovarian carcinoma cell lines. Jones, J., Lagasse, L.D., Karlan, B.Y. Gynecol. Oncol. (1994) [Pubmed]
  13. Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor. Salicioni, A.M., Xi, M., Vanderveer, L.A., Balsara, B., Testa, J.R., Dunbrack, R.L., Godwin, A.K. Genomics (2000) [Pubmed]
  14. Cloning, structure, and expression of the mouse Ovca1 gene. Chen, C.M., Behringer, R.R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  15. Characterization of the CA 125 antigen associated with human epithelial ovarian carcinomas. Davis, H.M., Zurawski, V.R., Bast, R.C., Klug, T.L. Cancer Res. (1986) [Pubmed]
  16. Role of endothelin-1 in neovascularization of ovarian carcinoma. Salani, D., Di Castro, V., Nicotra, M.R., Rosanò, L., Tecce, R., Venuti, A., Natali, P.G., Bagnato, A. Am. J. Pathol. (2000) [Pubmed]
  17. Proteinase requirements of epidermal growth factor-induced ovarian cancer cell invasion. Ellerbroek, S.M., Hudson, L.G., Stack, M.S. Int. J. Cancer (1998) [Pubmed]
  18. OVCA2 is downregulated and degraded during retinoid-induced apoptosis. Prowse, A.H., Vanderveer, L., Milling, S.W., Pan, Z.Z., Dunbrack, R.L., Xu, X.X., Godwin, A.K. Int. J. Cancer (2002) [Pubmed]
  19. Hormonal regulation of CA125 tumor marker expression in human ovarian carcinoma cells: inhibition by glucocorticoids. Karlan, B.Y., Amin, W., Casper, S.E., Littlefield, B.A. Cancer Res. (1988) [Pubmed]
  20. Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells. Syed, V., Ulinski, G., Mok, S.C., Yiu, G.K., Ho, S.M. Cancer Res. (2001) [Pubmed]
  21. Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor 2. Nobukuni, Y., Kohno, K., Miyagawa, K. J. Biol. Chem. (2005) [Pubmed]
  22. Identification of two candidate tumor suppressor genes on chromosome 17p13.3. Schultz, D.C., Vanderveer, L., Berman, D.B., Hamilton, T.C., Wong, A.J., Godwin, A.K. Cancer Res. (1996) [Pubmed]
  23. Deletion mapping on chromosome 17p in medulloblastoma. Steichen-Gersdorf, E., Baumgartner, M., Kreczy, A., Maier, H., Fink, F.M. Br. J. Cancer (1997) [Pubmed]
  24. Down-regulation of the Diphthamide biosynthesis protein 2-like gene during retinoid-induced differentiation and apoptosis: implications against its tumor-suppressor activity. Liu, G., Wu, M., Levi, G., Ferrari, N. Int. J. Cancer (2000) [Pubmed]
  25. Progesterone-induced apoptosis in immortalized normal and malignant human ovarian surface epithelial cells involves enhanced expression of FasL. Syed, V., Ho, S.M. Oncogene (2003) [Pubmed]
  26. Transfection of human ovarian cancer cells with the HER-2/neu receptor tyrosine kinase induces a selective increase in PTP-H1, PTP-1B, PTP-alpha expression. Wiener, J.R., Kassim, S.K., Yu, Y., Mills, G.B., Bast, R.C. Gynecol. Oncol. (1996) [Pubmed]
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