Studies of low basal Jun N-terminal kinase (JNK) activity in non-stressed cells led us to identify a JNK inhibitor that was purified and identified as glutathione S-transferase
Stress-activated signaling cascades are a ected by altered redox potential. Key contributors to altered redox potential are reactive oxygen species (ROS) which are formed, in most cases, by exogenous genotoxic agents including irradiation, in¯ammatory cytokines and chemical carcinogens. ROS and altered redox potential can be considered as the primary intracellular changes which regulate protein kinases, thereby serving as an important cellular component linking external stimuli with signal transduction in stress response. The mechanisms, which underlie the ROS-mediated response, involve direct alteration of kinases and transcription factors, and indirect modulation of cysteine-rich redox-sensitive proteins exempli®ed by thioredoxin and glutathione Stransferase. This review summarizes the current understanding of the mechanisms contributing to ROS-related changes in key stress activated signaling cascades.
In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount of p53-JNK complex was inversely correlated with p53 level. A peptide corresponding to the JNK binding site on p53 efficiently blocked ubiquitination of p53. Similarly, p53 lacking the JNK binding site exhibits a longer half-life than p53 wt . Outcompeting JNK association with p53 increased the level of p53, whereas overexpression of a phosphorylation mutant form of JNK inhibited p53 accumulation. JNK-p53 and Mdm2-p53 complexes were preferentially found in G 0 /G 1 and S/G 2 M phases of the cell cycle, respectively. Altogether, these data indicate that JNK is an Mdm2-independent regulator of p53 stability in nonstressed cells.
Our in vitro studies showed that up-regulation of miR-491-5p suppressed proliferation of the human osteosarcoma cells and induced apoptosis by targeting FOXP4. These findings suggest that miR-491-5p could be further studied as a potential clinical diagnostic or predictive biomarker for human osteosarcoma.
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