2018 Fiscal Year Final Research Report
Analysis of a novel regulatory mechanism "CLIP Model" of CDC-48, a AAA chaperone
| Project/Area Number |
16K08594
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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 |
General medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-10-21 – 2019-03-31
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| Keywords | 分子シャペロン / 線虫 |
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| Outline of Final Research Achievements |
I found that both N and PUB domains, especially the PUB domain, of UBXN-6 are important for the interaction with CDC-48. In the mutant worms containing the PUB-domain-lacking UBXN-6, mutant UBXN-6 was not detected by Western blotting. Interestingly, it was however detected when the worms were treated with the proteasome inhibitor. These results suggested that the PUB-domain-lacking UBXN-6 can not properly interact with CDC-48 and free UBXN-6 molecules were degraded by the proteasome. This notion strongly supports the Clip model. I also found that the amount of UBXN-6 was increased upon starvation and that UBXN-6 is involved in the formation of late endosomes.
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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 |
UBXN-6とCDC-48の相互作用様式を明らかにし、提唱した「クリップモデル」を支持する結果を得た。UBXN-6欠損株は短寿命を示すことも観察しており、これは細胞内タンパク質品質管理不全が一因となっている可能性が示唆された。CDC-48の変異に起因するヒト遺伝性疾患ALSやIBMPFDも知られており、タンパク質品質管理という観点からも今回得られた結果は、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期待される。
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