Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently cloned ATM gene has been shown to bear considerable homology to phosphatidylinositol 3 kinases and, therefore, its product may function in signal transduction. In this study, we report constitutively elevated levels of two IFN-beta-inducible proteins, ubiquitin cross-reactive protein (UCRP), and low molecular weight protein (LMP2), in human fibroblasts with the inherited disease ataxia telangiectasia (AT). Using immunoblotting, it was found that a M(r) 15,000 band representing free UCRP was hardly detectable in normal cells, while it was the predominant band in AT cells. Similarly, the expression of a M(r) 23,000 protein, LMP2 was found to be higher in AT cells than in normal cells. Culturing three successive passages of the AT cell line in the presence of different concentrations of neutralizing antibodies against IFN-beta caused partial and complete reduction, respectively, of the free UCRP and LMP2 signals to normal levels. These results indicate that UCRP and LMP2 pools may be basally elevated in AT cells due to constitutive activation of the IFN-beta induction pathway and are in keeping with the recently reported constitutive activation of the NF-kappaB transcriptional activator in AT cells.
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PMID:Elevation of interferon beta-inducible proteins in ataxia telangiectasia cells. 856 49

Cellular senescence is reportedly involved in cholangiopathy in primary biliary cirrhosis and oxidative stress is proposed as a pathogenetic factor in biliary epithelial cells (BECs). This study investigated the involvement of proinflammatory cytokines (IFN-beta, IFN-gamma and TNF-alpha) and ataxia telangiectasia-mutated (ATM)/p53/ p21(WAF1/Cip1) pathway with respect to oxidative stress in cellular senescence of BECs. H(2)O(2) treatment (oxidative stress) induced phosphorylation (activation) of ATM and p53 and also p21(WAF1/Cip1) expression in BECs. Treatment with inflammatory cytokines generated reactive oxygen species (ROS) in cultured BECs followed by activation of the ATM/p53/p21(WAF1/Cip1) pathway and the induction of cellular senescence. Pre-treatment with ATM inhibitor (2-aminopurine) and antioxidant (N-acetylcysteine) significantly blocked the cellular senescence of BECs induced by oxidative stress or inflammatory cytokines. In conclusion, proinflammatory cytokines induce ROS generation and activate the ATM/p53/p21(WAF1/Cip1) pathway, followed by biliary epithelial senescence. This senescent process may be involved in the development of destructive cholangiopathy in humans.
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PMID:Proinflammatory cytokine-induced cellular senescence of biliary epithelial cells is mediated via oxidative stress and activation of ATM pathway: a culture study. 1860 17