E3 ligase recruitment by UBQLN2 protects substrates from proteasomal degradation.

ABSTRACT: Ubiquilins are a family of proteins critical to cellular proteostasis that are also linked to several neurodegenerative diseases, with specific mutations in UBQLN2 causing dominant, X-linked ALS. Despite an initial characterization as proteasomal shuttle factors, Ubiquilins have paradoxically been reported to stabilize numerous substrates. The basis of this triage decision remains enigmatic. Many other fundamental aspects of Ubiquilin function are unclear at the mechanistic level, such as the physiological significance of Ubiquilin phase separation, the unique role of each Ubiquilin paralog, and the mechanistic defects of ALS mutants. To address these questions, we utilized a library of triple knockout (TKO) rescue cell lines with physiological expression of single Ubiquilin paralogs or di

SUBMITTER: Scheutzow AN 

PROVIDER: S-EPMC12236894 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature