Functional characterization of a novel TSH receptor mutation (V711fs) with protein instability
| Project/Area Number |
24791087
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
NARUMI Satoshi 慶應義塾大学, 医学部, 特任助教 (40365317)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 先天性甲状腺機能低下症 / TSH受容体 / 変異 / たんぱく質不安定性 / プロテアソーム / ゲノム / 遺伝子 / たんぱく質 / 小児科学 / 遺伝学 / 内分泌学 / 分子生物学 / ホルモン / 受容体 |
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| Outline of Final Research Achievements |
We analyzed a TSH receptor mutation V711FfsX18, which was observed in a patient with congenital hypothyroidism. This mutation was subject to proteasome-dependent protein degradation. Two models were considered as a explanation for the protein instability of the mutation: Model 1, Loss of intact 54 aa C-terminal sequence; Model 2, Acquisition of frame-shifted 17 aa sequence. The result of cAMP-generating activity of the V711X mutation, which was comparable to wildtype, excluded the Model 1. When the 17-aa sequence was fused to the green fluorescent protein or the luciferase protein, remarkable reduction in their activities were shown. Based on these observations, we concluded that acquisition of 17-aa frame-shifted sequence causes the protein instability of the V711FfsX TSH receotor mutation.
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Report
(4 results)
Research Products
(6 results)
