title: Ubiquitin C-terminal hydrolase L1 (UCH-L1): structure, distribution and roles in brain function and dysfunction.
abstract: Ubiquitin C-terminal hydrolase L1 (UCH-L1) is an extremely abundant protein in the brain where, remarkably, it is estimated to make up 1-5% of total neuronal protein. Although it comprises only 223 amino acids it has one of the most complicated 3D knotted structures yet discovered. Beyond its expression in neurons UCH-L1 has only very limited expression in other healthy tissues but it is highly expressed in several forms of cancer. Although UCH-L1 is classed as a deubiquitinating enzyme (DUB) the direct functions of UCH-L1 remain enigmatic and a wide array of alternative functions has been proposed. UCH-L1 is not essential for neuronal development but it is absolutely required for the maintenance of axonal integrity and UCH-L1 dysfunction is implicated in neurodegenerative disease. Here we review the properties of UCH-L1, and how understanding its complex structure can provide new insights into its roles in neuronal function and pathology.
authors: School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, U.K.
authors: Paul
authors: P
authors: Bishop
authors: School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, U.K.
authors: Dan
authors: D
authors: Rocca
authors: School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, U.K. j.m.henley@bristol.ac.uk.
authors: Jeremy M
authors: JM
authors: Henley
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D011487:Protein Conformation; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000378:metabolism*
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
keywords: axon; neurites; ubiquitin C-terminal hydrolase L1 (UCH-L1); ubiquitin ligases; ubiquitin proteasome system