TRIM9 and TRIM26 Interact with UBQLN2^P497H to Modulate Its Proteasomal Degradation.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss. ALS-linked mutations in UBQLN2 promote protein aggregation and disrupt proteostasis, yet the mutation-specific protein interactomes and their functional relevance remain poorly defined. We employed APEX2 proximity labeling, together with affinity enrichment of biotinylated peptides and LC-MS/MS analysis, to profile the interactomes of wild-type UBQLN2 and two ALS-linked variants, UBQLN2^P497H and UBQLN2^P497S. We identified 785 unique biotinylated proteins, many of which exhibit augmented enrichment in the proximity proteomes of the two mutants over wild-type UBQLN2. Notably, the E3 ubiquitin ligases TRIM9 and TRIM26 were selectively enriched in the

SUBMITTER: Chen X 

PROVIDER: S-EPMC12867519 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature