UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.

ABSTRACT: Protein-lipid crosstalk is fundamental to homeostasis in the endoplasmic reticulum (ER). The ER-associated degradation (ERAD) pathway, a branch of the ubiquitin-proteasome system, maintains ER membrane properties by degrading lipid metabolic enzymes. However, the ERAD components that sense membrane properties and their mechanisms remain poorly defined. Using reconstituted systems with purified ERAD factors, we show that membrane composition modulates the ubiquitination cascade at multiple levels. The membrane-anchored E2 UBE2J2 acts as a sensor for lipid packing: in loosely packed membranes, UBE2J2 becomes inactive due to membrane association that impedes ubiquitin loading, while tighter packing promotes its active conformation and interaction with E1. UBE2J2 activity directs ubiquitin tra

SUBMITTER: Vrentzou A 

PROVIDER: S-EPMC12511567 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature