title: Ubiquilin 2: a component of the ubiquitin-proteasome system with an emerging role in neurodegeneration.
abstract: Ubiquilin 2, which is encoded by the UBQLN2 gene, plays a critical role in protein clearance pathways including the ubiquitin-proteasome system and autophagy. Ubiquilin 2 physically associates with ubiquitin ligases and proteasomes to mediate protein degradation. It also plays a role in the regulation of cell signalling and cell cycle progression, and association with cytoskeletal elements. Recent studies have revealed that ubiquilin 2 also plays a pathogenic role in neurodegenerative disease, including amyotrophic lateral sclerosis (ALS), and ALS-frontotemporal dementia (ALS-FTD). Rare UBQLN2 mutations cause a small subset of ALS and ALS-FTD cases. More widespread is the presence of ubiquilin 2 positive inclusions in the affected neurons of some familial and sporadic ALS and ALS-FTD patients. These discoveries have led to the hypothesis that perturbation in protein clearance, mediated by ubiquilin 2, is an important pathogenic mechanism in neurodegeneration.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors.forename: Katharine Y
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
authors.forename: Sadaf T
authors.initials: ST
authors.lastname: Warraich
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia. Electronic address: ian.blair@mq.edu.au.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Blair
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D003704:Dementia / Q000209:etiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex
keywords: Amyotrophic lateral sclerosis; Autophagy; Dementia; Ubiquilin 2; Ubiquitin–proteasome system