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論文
- タイトル
- タイトル（英）
- Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins.
- 参照URL
- https://researchmap.jp/tsuchiya-hk/published_papers/53617597
- 著者
- 著者（英）
- Satoko Komatsu-Hirota,Keisuke Tabata,Yu-Shin Sou,Soichiro Kakuta,Jun-Ichi Sakamaki,Hikaru Tsuchiya,Jiachen Li,Hiroyuki Kumeta,Yuji Sakai,Yuko Fujioka,Daisuke Noshiro,Shunsuke F Shimobayashi,Tomo Kurimura,Takashi Taniguchi,Manabu Abe,Masato Koike,Hideaki Morishita,Nobuo N Noda,Masaaki Komatsu
- 担当区分
- 概要
- 概要（英）
- p62/SQSTM1 self-assembles with polyubiquitin into liquid-like condensates ("p62 bodies") that function as stress-signaling hubs and selective autophagy cargo. We show that TBK1-dependent phosphorylation at Ser403 acts as a threshold-dependent modulator of a condensate's physical properties and promotes their rapid autophagic clearance. Phosphorylation within p62 bodies drives a transition from large, fluid droplets to compact, gel-like condensates that efficiently capture LC3-positive isolation membranes and accelerate the autophagic removal of ubiquitinated proteins. PP2A holoenzymes containing PPP2R5A/B/E, recruited via a KEAP1 bridge, counteract TBK1 by dephosphorylating Ser403. Homozygous p62S403E/S403E knock-in embryonic stem cells differentiate into post-mitotic neurons enriched in miniaturized, gel-like p62 bodies. Consistently, phosphorylation-mimetic knock-in mice show similar remodeling of p62 condensates in vivo, demonstrating that this phosphorylation-driven mechanism maintains proteostasis across scales. We propose that Ser403 phosphorylation functions as a molecular switch that couples the material state of p62 condensates to their stability and serves as a central control point for p62-mediated protein degradation.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- The EMBO journal
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2026年5月5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/10.1038/s44318-026-00785-1
- 共同研究・競争的資金等の研究課題
研究者
土屋 光
( )