title: The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.
abstract: YOD1 is a highly conserved deubiquitinating enzyme of the ovarian tumor (otubain) family, whose function has yet to be assigned in mammalian cells. YOD1 is a constituent of a multiprotein complex with p97 as its nucleus, suggesting a functional link to a pathway responsible for the dislocation of misfolded proteins from the endoplasmic reticulum. Expression of a YOD1 variant deprived of its deubiquitinating activity imposes a halt on the dislocation reaction, as judged by the stabilization of various dislocation substrates. Accordingly, we observe an increase in polyubiquitinated dislocation intermediates in association with p97 in the cytosol. This dominant-negative effect is dependent on the UBX and Zinc finger domains, appended to the N and C terminus of the catalytic otubain core domain, respectively. The assignment of a p97-associated ubiquitin processing function to YOD1 adds to our understanding of p97's role in the dislocation process.
authors.affiliation: Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ernst
authors.forename: Britta
authors.initials: B
authors.lastname: Mueller
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: Christian
authors.initials: C
authors.lastname: Schlieker
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D020134:Catalytic Domain / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D010450:Endopeptidases / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000502:physiology*; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics; D000074405:Valosin Containing Protein; D016335:Zinc Fingers / Q000502:physiology; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C487709:DERL1 protein, human; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D025801:Ubiquitin; D000515:alpha 1-Antitrypsin; C034241:ribophorin; C545663:YOD1 protein, human; D013869:Thiolester Hydrolases; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein