Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins

ABSTRACT: 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 m

SUBMITTER: Satoko Komatsu-Hirota 

PROVIDER: S-SCDT-10_1038-S44318-026-00785-1 | biostudies-other |

REPOSITORIES: biostudies-other