title: Uch2/Uch37 is the major deubiquitinating enzyme associated with the 26S proteasome in fission yeast.
abstract: Conjugation of proteins to ubiquitin plays a central role for a number of cellular processes including endocytosis, DNA repair and degradation by the 26S proteasome. However, ubiquitination is reversible as a number of deubiquitinating enzymes mediate the disassembly of ubiquitin-protein conjugates. Some deubiquitinating enzymes are associated with the 26S proteasome contributing to and regulating the particle's activity. Here, we characterise fission yeast Uch2 and Ubp6, two proteasome associated deubiquitinating enzymes. The human orthologues of these enzymes are known as Uch37 and Usp14, respectively. We report that the subunit Uch2/Uch37 is the major deubiquitinating enzyme associated with the fission yeast 26S proteasome. In contrast, the activity of Ubp6 appears to play a more regulatory and/or structural role involving the proteasome subunits Mts1/Rpn9, Mts2/Rpt2 and Mts3/Rpn12, as Ubp6 becomes essential when activity of these subunits is compromised by conditional mutations. Finally, when the genes encoding Uch2/Uch37 and Ubp6 are disrupted, the cells are viable without showing obvious signs of impaired ubiquitin-dependent proteolysis, indicating that other deubiquitinating enzymes may remedy for the redundancy of these enzymes.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU Scotland, UK.
authors.forename: Miranda
authors.initials: M
authors.lastname: Stone
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
authors.forename: Michael
authors.initials: M
authors.lastname: Seeger
authors.forename: Dawadschargal
authors.initials: D
authors.lastname: Bech-Otschir
authors.forename: Mairi
authors.initials: M
authors.lastname: Wallace
authors.forename: Colin
authors.initials: C
authors.lastname: Gordon
mesh_terms: D002268:Carboxypeptidases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D002268:Carboxypeptidases; C421245:UCHL5 protein, human; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease