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Study on the regulation of the type 1 interferon signaling mediated by viral nucleic acids : 바이러스 핵산에 의한 제 1형 인터페론 신호전달 조절에 관한 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 안광석 | - |
dc.contributor.author | 서민지 | - |
dc.date.accessioned | 2017-07-14T00:53:38Z | - |
dc.date.available | 2017-07-14T00:53:38Z | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000141998 | - |
dc.identifier.uri | https://hdl.handle.net/10371/121465 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 안광석. | - |
dc.description.abstract | The innate immune system detects viral nucleic acids and induces
type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-β production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1–TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubuleassociated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling. | - |
dc.description.tableofcontents | INTRODUCTION 1
1. Type I IFN signaling 1 2. Butyrophilin (BTN) family 5 3. Microtubule associated proteins and motor proteins 9 RESULTS 10 1. Identification and characterization of BTN3A1 as a novel regulator of type I IFN responses 10 2. BTN3A1 regulates the phosphorylation of IRF3 30 3. BTN3A1 directs the interaction of TBK1 with IRF3 56 4. Microtubule-dependent transport of BTN3A1 to the perinuclear region 72 5. MAP4 is essential for type I IFN signaling by controlling the trafficking of BTN3A1 82 6. BTN3A1 interacts with dynein for trafficking to the perinuclear region 102 DISCUSSION 108 EXPERIMENTAL PROCEDURES 111 REFERENCES 119 ABSTRACT IN KOREAN 125 | - |
dc.format | application/pdf | - |
dc.format.extent | 4664948 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | TYPE I IFN | - |
dc.subject | BTN3A1 | - |
dc.subject | MAP4 | - |
dc.subject | TBK1-IRF3 AXIS | - |
dc.subject.ddc | 570 | - |
dc.title | Study on the regulation of the type 1 interferon signaling mediated by viral nucleic acids | - |
dc.title.alternative | 바이러스 핵산에 의한 제 1형 인터페론 신호전달 조절에 관한 연구 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | 128 | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2017-02 | - |
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