Gene interactions and pathways from curated databases and text-mining
Nucleosides Nucleotides Nucleic Acids 2010, PMID: 20544543

Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma.

Wan, Laxiang; Cao, Deliang; Zeng, Jianmin; Ziemba, Amy; Pizzorno, Giuseppe

Uridine phosphorylase (UPase) has been shown to be induced in various human and murine tumors and could potentially serve as a specific target for the modulation of tumor-selectivity of fluoropyrimidines. However, the signaling mechanisms underlying the regulation of UPase gene expression have not been determined. In this study, we investigated the effects of IFN-gamma on the regulation of TNF-alpha-induced UPase activity and have uncovered the molecular mechanisms of this potentiation, utilizing murine EMT6 breast cancer cells. Our data has shown that IFN-gamma can significantly increase UPase mRNA expression and the enzymatic activity induced by TNF-alpha in a dose-dependent manner, resulting in an enhanced sensitivity to 5-fluorouracil (5-FU) and 5'-Deoxy-5-fluorouridine (5'DFUR). We have previously shown that TNF-alpha activates NF-kappaB through increased translocation of NF-kappaB p65 from the cytoplasm into the nuclei. Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter. Notably, the activation of NF-kappaB and STAT1 in human breast tissues is consistent with UPase activity; signifying their role in the up-regulation of the UPase gene expression in human tumors.

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Text Mining Data

uridine phosphorylase → Stat1: " Activation of Stat1 , IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

uridine phosphorylase → tumor necrosis factor-alpha: " Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

uridine phosphorylase → IRF-1: " Activation of Stat1, IRF-1 , and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

uridine phosphorylase → interferon-gamma: " Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

uridine phosphorylase → IRF-1: " Activation of Stat1, IRF-1 , and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

uridine phosphorylase → NF-kappaB: " Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma "

STAT1 ⊣ p65: " Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter "

STAT1 ⊣ NF-kappaB: " Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter "

p65 ⊣ IRF-1: " Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter "

IRF-1 ⊣ NF-kappaB: " Exposure to IFN-gamma mainly affects nuclear IRF-1 and STAT1 in EMT6, but inhibits NF-kappaB p65 activity, indicating that the cooperative stimulation was the result of the independent activation of NF-kappaB, STAT1 and IRF-1 transcriptional factors through binding to their unique sites in the UPase promoter "

Manually curated Databases

No curated data.