| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
To clarify the mechanism of gp130, a common cytokine signal transducer for the Interleukin-6 family of cytokines, and downstream Stat3 signaling in the induction of cellular senescence, we identified a new modification site on Stat3 by mass spectrometry-based proteomic analysis. Mutation at this site partially affected target gene expression. To elucidate the detailed mechanism, affinity-purified polyclonal antibodies recognizing the novel STAT3 modification site were generated and revealed it works under certain conditions. The results suggest that Stat3 signaling may act directly on transcriptional activation of the IGFBP5 gene, a molecule that exerts its function downstream of gp130-Stat3 in normal diploid cells. We found a group of senescence-associated effector molecules that were induced downstream of gp130-Stat3 signaling and revealed that they might act cooperatively in the induction of cellular senescence.
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