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Gene Review

NUDT6  -  nudix (nucleoside diphosphate linked...

Homo sapiens

Synonyms: ASFGF2, Antisense basic fibroblast growth factor, FGF-AS, FGF2AS, GFG-1, ...
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Disease relevance of NUDT6

  • However, one group was unable to detect bFGF RNA transcripts in human melanoma cells using a human complementary DNA probe [1].
  • Further analysis of the bFGF-induced expression of collagenase-3 in human chondrosarcoma cells revealed that its effect was time and dose dependent, but independent of the de novo synthesis of proteins [2].
  • However, the recruitment of leukocytes to inflammation induced by tumor necrosis factor-alpha, interferon-gamma, C5a, or a delayed hypersensitivity reaction was enhanced by bFGF by 55 to 132% (P < 0.05) [3].
  • Strand-specific gfg-1 complementary RNA probes detect a 1.5-kilobase mRNA transcript in normal rat tissues and human T47D breast cancer cells, which contain very low levels of bFGF mRNA [4].
  • We have previously reported that increased messenger RNA (mRNA) stability contributes to the elevated steady state levels of bFGF mRNA in human U87-MG glioma cells [4].

Psychiatry related information on NUDT6

  • Neuritic involvement within bFGF immunopositive plaques of Alzheimer's disease [5].
  • Within the critical period, c-Fos was dramatically elevated through 48 h after the lesion, while bFGF peaked later, on day 6 [6].
  • The young athletes showed increased angiogenin and endostatin levels and decreased bFGF levels after 45 min of intensive physical activity, whereas leptin levels were not altered [7].
  • Huntington's disease and neurogenesis: FGF-2 to the rescue [8]?

High impact information on NUDT6

  • Heparin-dependent mitogenic activity of bFGF is strongly augmented by perlecan [9].
  • These PIs also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol) [10].
  • Thus, inhibition of bFGF/FGFR-1-mediated signaling may open a new avenue for the treatment of advanced-stage melanomas [11].
  • Here we report that subretinal injection of bFGF results in extensive rescue of photoreceptors in RCS rats for at least two months after the injection, and that intravitreal injection of bFGF results in even more widespread rescue, across almost the entire retina [12].
  • Despite this copious production of bFGF, most of these tissues are not undergoing either active growth or angiogenesis, suggesting that bFGF activity must be regulated so as to prevent autostimulation of cell growth [13].

Chemical compound and disease context of NUDT6

  • CONCLUSIONS: These results suggested that suppression of bFGF expression in RPE cells might partly account for the inhibitive effect of genistein on retinal neovascularization in vivo [14].
  • RESULTS: In acetic acid-induced gastric ulcers in rats, rh-bFGF 2.5-40 i.g. accelerated the chronic ulcer healing with a bell-shaped dose-effect curve and the best dosage was 10 [15].
  • While some of these effects may be mediated by the bFGF-responsive endothelial cells of the tumor vasculature (DLD-2 colon carcinoma), others may result from inhibition of bFGF-dependent tumor cell proliferation (C6 glioma) [16].
  • Patients with ischemia had an increase in urine bFGF compared with nonischemic patients (1052 +/- 245 versus -278 +/- 130 pg/g creatinine, P < .0001) [17].
  • Only one bFGF isoform (17.8 kd) was found in idiopathic pulmonary fibrosis and chronic beryllium disease lung tissues and interacted with heparin-like molecules in the lung [18].

Biological context of NUDT6


Anatomical context of NUDT6

  • The data indicate that the stromal cells produce bFGF and that their extracellular matrix can serve as a reservoir for this growth factor [20].
  • In immunofluorescence experiments on BM and peripheral blood smears, megakaryocytes and platelets stained strongly for bFGF, whereas weaker staining was observed in immature and mature cells of the granulocyte series [20].
  • Members of high (22-, 22.5-, 24-, and 34-kDa) and low (18-kDa) molecular mass forms of fibroblast growth factor-2 (FGF-2) regulate cell proliferation, differentiation, and migration [21].
  • However, the expression of the endothelial cell adhesion molecules (CAMs) for leukocytes, P-selectin, E-selectin, and ICAM-1, was significantly up-regulated in the inflamed tissue by bFGF, as quantified by radiolabeled anti-CAM antibody binding in vivo [3].
  • Thus, although not directly proinflammatory, bFGF synergistically potentiates inflammatory mediator-induced leukocyte recruitment, at least in part, by enhancing CAM up-regulation on endothelium [3].

Associations of NUDT6 with chemical compounds


Physical interactions of NUDT6

  • The secondary FGFR binding site on bFGF has an approximately 250-fold lower affinity and is composed of amino acids Lys-110, Tyr-111, and Trp-114 in a surface-exposed type I beta-turn (formerly known as the putative receptor binding loop) [26].

Regulatory relationships of NUDT6

  • Isoproterenol inhibited the basal and bFGF-induced proliferation of HFMc through a MEK-1/2-independent pathway that included the accumulation of cAMP [24].
  • In confluent HFMc, bFGF (20 ng/mL) induced a significant 4-fold increase in ERK-2 activity and [3H]-thymidine incorporation (6-fold) [24].
  • In Western blot analysis, bFGF induced cytoplasmic translocation of p21(Waf1/Cip1) and p27(Kip1) and phosphorylation of p27(Kip1) but rk-2 treatment inhibited translocation of p21(Waf1/Cip1) and p27(Kip1) from nucleus to cytoplasm and phosphorylation of p27(Kip1) [27].
  • Interestingly, bFGF downregulated lysyl oxidase enzyme activity by 10% to 20% [28].
  • 4. In CHO-K1 cells stably expressing rat recombinant sst2 (r sst2) or sst5 (r sst5) receptors, SRIF (0.1-1000 nM) was able to inhibit the bFGF-stimulated re-growth (pIC50=7.98+/-24 and 8.50+/-0.12, respectively) [29].

Other interactions of NUDT6

  • Because bFGF induces collagenase-1 in most cell types, cell-specific expression of FGFR family members may dictate the regulation of matrix metalloproteinases in a tissue-specific manner [30].
  • However, KGF was >100-fold more effective than bFGF at inhibiting collagenase-1 expression, suggesting that this differential signaling is transduced via an FGF receptor that binds these ligands with different affinities [30].
  • Identification and characterization of an antisense RNA transcript (gfg) from the human basic fibroblast growth factor gene [4].
  • These data suggest that high molecular weight forms of bFGF overexpressed in MCF-7 cells do not activate the receptor-mediated MAP kinase pathway, and do not induce p21WAF1/CIP1 in an autocrine manner, but inhibit proliferation through other, possibly direct nuclear signalling mechanisms [31].
  • The accumulation of cAMP in HFMc counteracts the mitogenic effects of bFGF by a MEK-1/2-independent pathway [24].

Analytical, diagnostic and therapeutic context of NUDT6


  1. Differences in basic fibroblast growth factor RNA and protein levels in human primary melanocytes and metastatic melanoma cells. Yamanishi, D.T., Graham, M.J., Florkiewicz, R.Z., Buckmeier, J.A., Meyskens, F.L. Cancer Res. (1992) [Pubmed]
  2. Collagenase-3 (MMP-13) expression in chondrosarcoma cells and its regulation by basic fibroblast growth factor. Uría, J.A., Balbín, M., López, J.M., Alvarez, J., Vizoso, F., Takigawa, M., López-Otín, C. Am. J. Pathol. (1998) [Pubmed]
  3. Basic fibroblast growth factor (bFGF, FGF-2) potentiates leukocyte recruitment to inflammation by enhancing endothelial adhesion molecule expression. Zittermann, S.I., Issekutz, A.C. Am. J. Pathol. (2006) [Pubmed]
  4. Identification and characterization of an antisense RNA transcript (gfg) from the human basic fibroblast growth factor gene. Murphy, P.R., Knee, R.S. Mol. Endocrinol. (1994) [Pubmed]
  5. Neuritic involvement within bFGF immunopositive plaques of Alzheimer's disease. Cummings, B.J., Su, J.H., Cotman, C.W. Exp. Neurol. (1993) [Pubmed]
  6. The temporal patterns of c-Fos and basic fibroblast growth factor expression following a unilateral anteromedial cortex lesion. Buytaert, K.A., Kline, A.E., Montañez, S., Likler, E., Millar, C.J., Hernandez, T.D. Brain Res. (2001) [Pubmed]
  7. Serum levels of angioregulatory mediators in healthy individuals depend on age and physical activity: studies of angiogenin, basic fibroblast growth factor, leptin and endostatin. Bruserud, O., Grovan, F., Lindås, R., Blymke Møinichen, C., Osterhus, K.K. Scand. J. Clin. Lab. Invest. (2005) [Pubmed]
  8. Huntington's disease and neurogenesis: FGF-2 to the rescue? La Spada, A.R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis. Aviezer, D., Hecht, D., Safran, M., Eisinger, M., David, G., Yayon, A. Cell (1994) [Pubmed]
  10. HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. Sgadari, C., Barillari, G., Toschi, E., Carlei, D., Bacigalupo, I., Baccarini, S., Palladino, C., Leone, P., Bugarini, R., Malavasi, L., Cafaro, A., Falchi, M., Valdembri, D., Rezza, G., Bussolino, F., Monini, P., Ensoli, B. Nat. Med. (2002) [Pubmed]
  11. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Wang, Y., Becker, D. Nat. Med. (1997) [Pubmed]
  12. Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Faktorovich, E.G., Steinberg, R.H., Yasumura, D., Matthes, M.T., LaVail, M.M. Nature (1990) [Pubmed]
  13. Basic fibroblast growth factor fused to a signal peptide transforms cells. Rogelj, S., Weinberg, R.A., Fanning, P., Klagsbrun, M. Nature (1988) [Pubmed]
  14. Inhibitive effect of genistein on hypoxia-induced basic fibroblast growth factor expression in human retinal pigment epithelium cells. Pan, J.S., Zhu, H.J., Zhang, B., Li, H., Yan, H., Wang, B. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. (2006) [Pubmed]
  15. Effect of recombinant human basic fibroblast growth factor on stomach ulcers in rats and mice. Wang, J.Z., Wu, Y.J., Rao, C.M., Gao, M.T., Li, W.G. Zhongguo yao li xue bao = Acta pharmacologica Sinica. (1999) [Pubmed]
  16. Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. Gross, J.L., Herblin, W.F., Dusak, B.A., Czerniak, P., Diamond, M.D., Sun, T., Eidsvoog, K., Dexter, D.L., Yayon, A. J. Natl. Cancer Inst. (1993) [Pubmed]
  17. Basic fibroblast growth factor as a biochemical marker of exercise-induced ischemia. Gu, J.W., Santiago, D., Olowe, Y., Weinberger, J. Circulation (1997) [Pubmed]
  18. Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders. Inoue, Y., King, T.E., Tinkle, S.S., Dockstader, K., Newman, L.S. Am. J. Pathol. (1996) [Pubmed]
  19. Characterization and tissue-specific expression of the rat basic fibroblast growth factor antisense mRNA and protein. Knee, R., Li, A.W., Murphy, P.R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  20. Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells. Brunner, G., Nguyen, H., Gabrilove, J., Rifkin, D.B., Wilson, E.L. Blood (1993) [Pubmed]
  21. Nuclear and nucleolar localization of 18-kDa fibroblast growth factor-2 is controlled by C-terminal signals. Sheng, Z., Lewis, J.A., Chirico, W.J. J. Biol. Chem. (2004) [Pubmed]
  22. Interaction of basic fibroblast growth factor (FGF-2) with nonresponsive HeLa cells. Gannoun-Zaki, L., Pieri, I., Badet, J., Barritault, D. Exp. Cell Res. (1994) [Pubmed]
  23. Heparin and heparan sulphate protect basic fibroblast growth factor from non-enzymic glycosylation. Nissen, N.N., Shankar, R., Gamelli, R.L., Singh, A., DiPietro, L.A. Biochem. J. (1999) [Pubmed]
  24. Angiotensin II and basic fibroblast growth factor mitogenic pathways in human fetal mesangial cells. Izevbigie, E.B., Gutkind, J.S., Ray, P.E. Pediatr. Res. (2000) [Pubmed]
  25. Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. II. The RAS/MAPK pathway and phosphorylation of BAD at serine 112. Gu, Q., Wang, D., Wang, X., Peng, R., Liu, J., Deng, H., Wang, Z., Jiang, T. Radiat. Res. (2004) [Pubmed]
  26. Identification and concerted function of two receptor binding surfaces on basic fibroblast growth factor required for mitogenesis. Springer, B.A., Pantoliano, M.W., Barbera, F.A., Gunyuzlu, P.L., Thompson, L.D., Herblin, W.F., Rosenfeld, S.A., Book, G.W. J. Biol. Chem. (1994) [Pubmed]
  27. Recombinant human prothrombin kringle-2 induces bovine capillary endothelial cell cycle arrest at G0-G1 phase through inhibition of cyclin D1/CDK4 complex: modulation of reactive oxygen species generation and up-regulation of cyclin-dependent kinase inhibitors. Kim, T.H., Oh, S., Kim, S.S. Angiogenesis (2005) [Pubmed]
  28. Cytokine regulation of gingival fibroblast lysyl oxidase, collagen, and elastin. Hong, H.H., Trackman, P.C. J. Periodontol. (2002) [Pubmed]
  29. Differential effects of somatostatin and angiopeptin on cell proliferation. Alderton, F., Lauder, H., Feniuk, W., Fan, T.P., Humphrey, P.P. Br. J. Pharmacol. (1998) [Pubmed]
  30. Cell type-specific inhibition of keratinocyte collagenase-1 expression by basic fibroblast growth factor and keratinocyte growth factor. A common receptor pathway. Pilcher, B.K., Gaither-Ganim, J., Parks, W.C., Welgus, H.G. J. Biol. Chem. (1997) [Pubmed]
  31. Overexpression of basic fibroblast growth factor in MCF-7 human breast cancer cells: lack of correlation between inhibition of cell growth and MAP kinase activation. Wieder, R., Fenig, E., Wang, H., Wang, Q., Paglin, S., Menzel, T., Gabrilove, J., Fuks, Z., Yahalom, J. J. Cell. Physiol. (1998) [Pubmed]
  32. Basic fibroblast growth factor secreted by an animal tumor is detectable in urine. Soutter, A.D., Nguyen, M., Watanabe, H., Folkman, J. Cancer Res. (1993) [Pubmed]
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