Role of STAT3 in cytokine-induced senescence
| Project/Area Number |
25460392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka City University |
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Principal Investigator |
Kojima Hirotada 大阪市立大学, 大学院医学研究科, 講師 (40336772)
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| Co-Investigator(Kenkyū-buntansha) |
中嶋 弘一 大阪市立大学, 大学院医学研究科, 教授 (00227787)
井上 敏昭 鳥取大学, 医学部, 准教授 (80305573)
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| Project Period (FY) |
2013-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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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| Keywords | サイトカイン / 細胞内情報伝達 |
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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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| Academic Significance and Societal Importance of the Research Achievements |
「サイトカイン」と呼ばれる主に糖タンパクからなる生体物質は，老化，恒常性，代謝系，免疫応答，神経系などの高次機能の発揮に重要な働きをもつ物質である。またその機能の破綻ががんや自己免疫など様々な疾患に繋がることがある。疾患の機序解明や治療法の開発には細かな分子レベルでの作用機序の理解が必要とされる。本研究で見いだされたサイトカインシグナル伝達分子Stat3の修飾の意義と、細胞老化制御における機序を発端として、新たなサイトカインシグナルの機序と役割の解明並びに制御法の開発に繋がっていくと考えられる。
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Report
(6 results)
Research Products
(7 results)
