2021 Fiscal Year Final Research Report
Analysis of CDC-48 defaulting by ASPS-1 and establishment of a novel nematode diabetes model
| Project/Area Number |
19K07371
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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 48040:Medical biochemistry-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | AAAシャペロン / 線虫 / 寿命 |
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| Outline of Final Research Achievements |
C. elegans ASPS-1 was found to interact with CDC-48 both in vivo and in vitro, but no heterotetramer formation was observed. ASPS-1-deficient strains were long-lived, but longevity was inhibited by introduction of DAF-18 (PTEN homologue) deficient mutation or MPZ-1 (PDZ domain protein) deficient mutation, suggesting that ASPS-1 utilizes PDZ domain proteins, which are scaffold proteins, to capture substrates. We also newly found that ASPS-1-deficient strains lost chemotaxis to diacetyl, while introduction of an ARR-1-deficient mutation restored chemotaxis.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
今回明らかにした寿命との関連、細胞増殖制御因子PTENとの相互作用ならびに匂い感知経路との関連などは、いまだに報告されたことがない極めてユニークかつ重要な機能である。p97の発現（活性）とがんの予後との関連性が報告されている。ASPS-1と相互作用するDAF-18/PTENは、細胞増殖を制御する極めて重要な因子である。CDC-48は、ALSやIBMPFDなどのヒト遺伝性疾患の原因因子でもある。これらを総合すると、CDC-48をベースにした種々のヒト疾患の診断・予防・治療戦略の確立や創薬研究の基盤となることが大いに期待される。
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