2023 Fiscal Year Final Research Report
Elucidation of the cell death evasion mechanism of cancer cells regulated by protein kinase c signaling
| Project/Area Number |
20K07289
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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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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | プロテインキナーゼC / スフィンゴシン1-リン酸 |
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| Outline of Final Research Achievements |
In this study, for elucidating the full extent of sphingosine 1-phosphate (S1P)-atypical protein kinase C (aPKC) signaling regulation in apoptosis resistance in cancer cells, we aimed to elucidate the downstream signals of S1P-aPKC and its relation with stress, and also clarify the structural and molecular mechanism of S1P-aPKC activation. As a result, we have got successful to find a post-translational modification of aPKC as a new molecular mechanism for S1P-induced aPKC activation and identify transcriptional factor X as an apoptosis-related molecule that acts downstream of S1P-aPKC signaling, and further identify a new starvation stress-related molecule involved in apoptosis resistance of cancer cells by S1P-aPKC signaling.
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| Free Research Field |
シグナル伝達
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果のポイントは、S1PによるaPKC活性化の分子メカニズムとして、翻訳後修飾の関与という全く新たな構造学的知見を見出した点である。本研究の成果により、アポトーシスのブレーキ役としてのS1P-aPKCシグナリングを分子レベルで制御する、新たながん治療法開発の実現に向けて新たな道筋が示された。今後は、S1P-aPKCシグナリングが転写因子Xを活性化しアポトーシスを抑制するシグナル伝達の全容解明を目指すとともに、リード化合物の創出を目指した分子標的創薬の研究を平行して推進する。
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