Epidermal growth factor suppresses interferon-induced accumulation of p53 and p21 by using protein kinase C.
The tumor suppressor protein p53 is the most frequently mutated gene in human cancers. Since its discovery, p53 has evolved from a potential oncogene to the principal tumor suppressor in humans. p53 protects not only against oncogenic stress but also against the presence of DNA damage. Now, p53 is positioned at the vertex of cellular signals warning of threats of genomic damage and oxidative stress. Under these conditions p53 is phosphorylated by multiple kinases and these phosphorylations not only increase its half-life but also increase its localization in the nucleus. p53 localized in the nucleus induces cell-cycle arrest to allow repair processes or, failing that, promotes cellular senescence or cell death. In this study it is shown that treatment of ME180S cells with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) result in time-dependent accumulation of p53 and its transcriptional target, p21. Pretreatment of ME180S cells with epidermal growth factor (EGF) inhibits IFN-dependent induction of p53 and p21 by protein kinase C dependent pathways.
Akca
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Department of Biology, Faculty of Art and Science, Akdeniz University, Arapsuyu/Antalya, Turkey.
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D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism*
C493956:CDKN1A protein, human; D002867:Chromones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D016898:Interferon-alpha; D008301:Maleimides; D009025:Morpholines; D016159:Tumor Suppressor Protein p53; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D007372:Interferons; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one