title: Ubiquitin dimers control the hydrolase activity of UCH-L3.
abstract: Ubiquitin (Ub) carboxy terminal hydrolase (UCH)-L1 and UCH-L3 are two of the deubiquitinating enzymes expressed in the brain. Both gad mice, which lack UCH-L1 expression and Uchl3 knockout mice exhibit neurodegeneration, although at distinct areas. These phenotypes indicate the importance of UCH-L1 and UCH-L3 in the regulation of the central nervous system. However, molecular substrates and the molecular regulators of UCH-L1 and UCH-L3 remain poorly identified. Here we show that Ub dimers interact non-covalently with UCH-L3 in vitro and in cells. These interactions were not observed with UCH-L1 in cells. In vitro, K48-linked Ub dimers pronouncedly inhibited the hydrolase activity of UCH-L3, while mono-Ub, a previously identified interacting protein, inhibited the hydrolase activity of UCH-L1. These results indicate that mono-Ub and Ub dimers may regulate the enzymatic functions of UCH-L1 and UCH-L3, respectively, in vivo.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Ogawahigashi, Kodaira, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Setsuie
authors.forename: Mikako
authors.initials: M
authors.lastname: Sakurai
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005260:Female; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C482860:UCHL1 protein, human; D025801:Ubiquitin; D006867:Hydrolases; C509806:UCHL3 protein, human; D043222:Ubiquitin Thiolesterase; D003546:Cysteine Endopeptidases