Browse

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

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
서민지
Advisor
안광석
Major
자연과학대학 생명과학부
Issue Date
2017-02
Publisher
서울대학교 대학원
Keywords
TYPE I IFNBTN3A1MAP4TBK1-IRF3 AXIS
Description
학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 안광석.
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.
Language
English
URI
https://hdl.handle.net/10371/121465
Files in This Item:
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Ph.D. / Sc.D._생명과학부)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse