Disease relevance of ZNF403

• Thus, these results suggest that DIF-3 may be a target gene mediating the reproductive toxicity induced by TCDD [1].

High impact information on ZNF403

• These results suggest that DIF-3 induces degradation of cyclin D1 through the GSK-3beta- and DYRK1B-mediated threonine phosphorylation in HeLa cells [2].
• We previously reported that DIF-3 activates glycogen synthase kinase-3beta (GSK-3beta), resulting in the degradation of cyclin D1 in HeLa cells [2].
• Although DIF-1 and DIF-3 both strongly inhibited cell proliferation by inducing G(0)/G(1) arrest, DIF-3 was more effective than DIF-1 [3].
• Indeed, DIF-3 dephosphorylated Ser(9) and phosphorylated tyrosine on GSK-3beta, and it stimulated GSK-3beta activity in an in vitro kinase assay [3].
• DIF-1 and some of its derivatives at nanomolar levels were good stalk-cell inducers in HM44 cells, whereas DIF-3 and some DIF-3 derivatives at micromolar levels were potent anti-proliferative agents in K562 cells [4].

Biological context of ZNF403

• Dioxin induces a novel nuclear factor, DIF-3, that is implicated in spermatogenesis [1].
• DIF-3 protein is a nuclear factor and possesses a zinc-finger motif at its N-terminus [1].
• Indeed, DIF-3 markedly elevated the phosphorylation level of cyclin D1, and mutations introduced to Thr(286) and/or Thr(288) prevented the phosphorylation induced by DIF-3 [2].
• It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells [4].
• It is suggested that the phenotype of IFN resistance of DIF8 and DIF9 cells may be related to a defect in receptor activation whereas the same phenotype of DIF3 cells would appear to be unrelated to IFN binding [5].

Anatomical context of ZNF403

• By means of the mRNA differential display method we identified a cDNA, Laryngeal carcinoma related gene 1 (LCRG1) which has significantly reduced expression in 40% (12/30) of primary LCs and in 6 of 10 various cancer cell lines [6].
• Northern Blot analysis showed that LCRG1 was expressed more abundantly in human heart, pancreas, skeletal muscle, and in murine testis, liver, brain and heart than in other tissues [6].

Associations of ZNF403 with chemical compounds

• In this study, we identified a novel TCDD target gene, DIF-3 (dioxin inducible factor-3), by cDNA representational difference analysis [1].
• No increase in cyclic GMP was observed in DIF2 or DIF3 cells treated with interferon-alpha [7].
• IC50 for PE-induced inhibition of DNA synthesis in estrogen-sensitive BC cells correlated with (MD*Log P) and Dif3 (3 chi-3 chi v difference index encoding nonsigma electronic charge of fragments consisting of four atoms and three bonds) and Dif3(2) [8].

Analytical, diagnostic and therapeutic context of ZNF403

• Molecular cloning and characterization of LCRG1 a novel gene localized to the tumor suppressor locus D17S800-D17S930 [6].
• Moreover, DIF-3 was revealed to induce the nuclear translocation of GSK-3beta by immunofluorescent microscopy and immunoblotting of subcellular protein fractions [3].
• METHODS: Two-dimensional gel electrophoresis (2-DE) technology was performed to separate the proteins of Hep-2/LCRG1 and Hep-2/pcDNA3.1(+) cell lines, respectively [9].

References