SEL1L degradation intermediates stimulate cytosolic aggregation of polyglutamine‐expanded protein

Misfolded proteins in the endoplasmic reticulum (ER) are degraded by ER-associated degradation (ERAD). In mammalian cells, HRD1–SEL1L membrane ubiquitin ligase complex plays a central role this process. However, SEL1L is inherently unstable, and excess also ERAD. Accordingly, when proteasome activity inhibited, multiple intermediates of appear cytosol. study, we searched for factors that inhibit identified OS-9 XTP3-B, two ER lectins regulate glycoprotein was characterized ladder products, C-terminal Pro-rich region responsible generation pattern. cytosol, these stimulated aggregation polyglutamine-expanded Huntingtin protein (Htt-polyQ-GFP) interacting with aggregation-prone proteins, including Htt-polyQ-GFP. Collectively, our findings indicate peptide fragments generated during ERAD may affect revealing interconnection homeostasis across subcellular compartments.