myxothiazol and pyrimidine

myxothiazol has been researched along with pyrimidine* in 1 studies

Other Studies

1 other study(ies) available for myxothiazol and pyrimidine

ArticleYear
Pyrimidine biosynthesis links mitochondrial respiration to the p53 pathway.
    Proceedings of the National Academy of Sciences of the United States of America, 2010, Jul-20, Volume: 107, Issue:29

    While many functions of the p53 tumor suppressor affect mitochondrial processes, the role of altered mitochondrial physiology in a modulation of p53 response remains unclear. As mitochondrial respiration is affected in many pathologic conditions such as hypoxia and intoxications, the impaired electron transport chain could emit additional p53-inducing signals and thereby contribute to tissue damage. Here we show that a shutdown of mitochondrial respiration per se does not trigger p53 response, because inhibitors acting in the proximal and distal segments of the respiratory chain do not activate p53. However, strong p53 response is induced specifically after an inhibition of the mitochondrial cytochrome bc1 (the electron transport chain complex III). The p53 response is triggered by the deficiency in pyrimidines that is developed due to a suppression of the functionally coupled mitochondrial pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH). In epithelial carcinoma cells the activation of p53 in response to mitochondrial electron transport chain complex III inhibitors does not require phosphorylation of p53 at Serine 15 or up-regulation of p14(ARF). Instead, our data suggest a contribution of NQO1 and NQO2 in stabilization of p53 in the nuclei. The results establish the deficiency in pyrimidine biosynthesis as the cause of p53 response in the cells with impaired mitochondrial respiration.

    Topics: Apoptosis; Cell Line, Tumor; Cell Respiration; Dihydroorotate Dehydrogenase; Electron Transport Complex III; Humans; Isoxazoles; Leflunomide; Membrane Potential, Mitochondrial; Methacrylates; Mitochondria; NAD(P)H Dehydrogenase (Quinone); Oxidoreductases Acting on CH-CH Group Donors; Potassium Cyanide; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Pyrimidines; Quinone Reductases; Reactive Oxygen Species; Signal Transduction; Thiazoles; Tumor Suppressor Protein p53; Up-Regulation

2010