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論文
- タイトル
- タイトル（英）
- CSNK2B modulates IRF1 binding to functional DNA elements and promotes basal and agonist-induced antiviral signaling.
- 参照URL
- https://researchmap.jp/dyamane/published_papers/42387095
- 著者
- 著者（英）
- Moe Matsumoto,Jennifer L Modliszewski,Kotomi Shinozaki,Reona Maezawa,Vincent M Perez,Yuki Ishikawa,Ryosuke Suzuki,Kevin L McKnight,Takahiro Masaki,Asuka Hirai-Yuki,Michinori Kohara,Stanley M Lemon,Sara R Selitsky,Daisuke Yamane
- 担当区分
- 概要
- 概要（英）
- Interferon regulatory factor 1 (IRF1) is a critical component of cell-intrinsic innate immunity that regulates both constitutive and induced antiviral defenses. Due to its short half-life, IRF1 function is generally considered to be regulated by its synthesis. However, how IRF1 activity is controlled post-translationally has remained poorly characterized. Here, we employed a proteomics approach to identify proteins interacting with IRF1, and found that CSNK2B, a regulatory subunit of casein kinase 2, interacts directly with IRF1 and constitutively modulates its transcriptional activity. Genome-wide CUT&RUN analysis of IRF1 binding loci revealed that CSNK2B acts generally to enhance the binding of IRF1 to chromatin, thereby enhancing transcription of key antiviral genes, such as PLAAT4 (also known as RARRES3/RIG1/TIG3). On the other hand, depleting CSNK2B triggered abnormal accumulation of IRF1 at AFAP1 loci, thereby down-regulating transcription of AFAP1, revealing contrary effects of CSNK2B on IRF1 binding at different loci. AFAP1 encodes an actin crosslinking factor that mediates Src activation. Importantly, CSNK2B was also found to mediate phosphorylation-dependent activation of AFAP1-Src signaling and exert suppressive effects against flaviviruses, including dengue virus. These findings reveal a previously unappreciated mode of IRF1 regulation and identify important effector genes mediating multiple cellular functions governed by CSNK2B and IRF1.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nucleic acids research
- 巻
- 51
- 号
- 9
- 開始ページ
- 4451
- 終了ページ
- 4466
- 出版年月
- 2023年5月22日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1093/nar/gkad298
- 共同研究・競争的資金等の研究課題
研究者
山根 大典
(ヤマネ ダイスケ)