Role of Ubiquilins in Neurodegenerative Diseases

Abstract

Ubiquilin (Ubqln) proteins, including Ubqln1-4, are a family of ubiquitin-like (UBL) proteins that structurally contain anN-terminalubiquitin-like domain, a C-terminalubiquitin-associated (UBA) domain, and aninternal variable number of Stil repeat motifs. Unlike those small molecule ubiquitin-like proteins, Ubqln proteins cannot be covalently tagged to the proteins that are targeted to the proteasome for degradation. Instead, this family of proteins binds to thepolyubiquitinated proteins via the UBA domain and delivers them to the proteasome for degradation, despite their involving in autophagy-mediated protein degradation. Increasing studies have suggested that Ubqln proteins play important roles in mediating the degradation of damaged/misfolded proteins and thus theirinsufficiencies or dysfunctionsare frequently associated with different neurodegenerative disorders. This review summarizes the role of Ubqln proteins in several neurodegenerative disorders.