Comprehension and application of biological information system based on the analysis of molecular mechanisms of stress response

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This research program aimed at disclosing the molecular mechanisms by which cells convert quantitative difference of signals into qualitative difference of responses. We investigated the stress responses with main focuses on the regulatory mechanisms of ASK family proteins by physico-chemical stresses. More concretely, following studies have been performed ; 1)oxidative stress- and endoplasmic reticulum stress-induced activation mechanisms of ASK1, 2)development of monitoring system of ASK1 activity, 3)search for small compounds which inhibit ASK1 activity, 4)activation mechanisms of ASK family proteins, 5)establishment of knockout mice of ASK family genes, 6)the effects of ASK1 gene deletion on the gene expression, protein modification and cell fate. Based on these experiments, we found that durations of activated proteins downstream of ASK1 play important roles in generation of qualitative differences of cellular responses. These excellent results suggested that the studies of stress responses through ASK family may lead to the development of revolutionary therapeutic drugs for neurodegenerative diseases and inflammation.