MARCH5에 의한 RIG-I/MAVS 신호전달의 조절

Alternative Title
Seong-Gwang Kim
Author(s)
김성광
Alternative Author(s)
Seong-Gwang Kim
Advisor
조혜성
Department
일반대학원 의생명과학과
Publisher
The Graduate School, Ajou University
Publication Year
2019-02
Language
eng
Alternative Abstract
The innate immune system has an important role in the mammalian immune response. Recent study has demonstrated that mitochondria take part in a broad range of innate immune pathways, functioning as signal platforms and resulting in activation of immune responses. Previously, our lab found that MARCH5 regulates immune response by resolving MAVS prion-like aggregates during viral infection. The present study revealed the kinetics of RIG-I/MAVS oligomerization upon poly(I:C) transfection. RIG-I and MAVS began to form oligomer, respectively after 12 hrs of poly(I:C) transfection. This was accompanied with accumulation of RIG-I and MAVS protein levels. At 36hrs after stimulation, the oligomerized RIG-I and MAVS proteins were accumulated in the NP_40-insoluble fractions, suggesting that the RIG-I/MAVS oligomers form a strong insoluble protein aggregates in cells. I found that MARCH5 not only targeted the oligomerized MAVS protein but also caused a significant reduction of the oligomerized RIG-I levels, of which degradation is mediated through a proteasome-dependent manner. In bone-marrow derived macrophage cell (BMDM) from MARCH5 knockout mice secreted high amount of type-I interferon secretion in response to poly(I:C) transfection. Approach to oligomeric complex provides understanding of relationship between RIG-I/MAVS oligomers and MARCH5. That make the reason I proposed that RIG-I and MAVS oligomers can be dual-targeted by MARCH5 during innate immune response.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/14959
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Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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