Global survey of endogenous substrates for Hero proteins upon proteostasis dysfunction and implication in anti-aggregation strategy.
| Project/Area Number |
22K14801
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
ChhipiShrestha Jagat 国立研究開発法人理化学研究所, 環境資源科学研究センター, 特別研究員 (40851233)
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| Project Period (FY) |
2022-04-01 – 2023-03-31
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| Project Status |
Discontinued (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | Hero-proteins / aggregation / proteostasis / Hero protein / protein aggregation |
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| Outline of Research at the Start |
Protein homeostasis is a vital factor to warrant human health and longevity. HEat Resistant Obscure (Hero) proteins have been identified as the factors which
prevents aggregation of several functional client proteins. Yet their substrates are largely unknown. The global suvery could reveal the promising insights on molecular role of Hero proteins in proteostasis balance and therapeutic application. Thus, here, the purpose of this project is to 1) investigate
aggregating proteome upon chaperone and UPS dysfunction, 2) understand aggregating client proteins of Hero proteins.
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| Outline of Annual Research Achievements |
Different chemical insults to mimic proteostatic disbalance such as Proteasome inhibition, autophagy inhibition and chaperone inhibition were used to induce the protein aggregation. Hero proteins were surveyed globally for their natural clients to potentially minimize the aggregation formation by their co-expression. Filter trap method was mostly used to investigate global aggregation and aggregating proteome wide study was extended by mass spectrometry. Top hit aggregating protein candidates which could be possibly co-localized with the Hero proteins were validated such as Hero9 might have essential function in stabilizing the candidate proteins in nucleolus to maintain the ribosome biogenesis. It is still the subject of study what properties of these aggregating proteins could be important for the action of Hero proteins for their disaggregation properties.
Yet number of other aggregating clients for each of the Hero proteins (Hero7, Hero9, Hero11, Hero13, Hero20, Hero45) were studied upon proteasome inhibition system-wide utilizing mass spectrometry after the filter trapping process. This technique is novel approach to study the aggregating proteins in system-wide manner which is essentially modified from the classical technique of filter trapping the aggregates. Further, the future study will imply for the mechanism of endogenous protein stabilization to relieve their potential aggregation and functionality of that proteins preventing the physiological disorders such as neurological disorders.
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Report
(1 results)
Research Products
(3 results)
