title: A Degenerate Cohort of Yeast Membrane Trafficking DUBs Mediates Cell Polarity and Survival.
abstract: Deubiquitinating enzymes (DUBs), cysteine or metallo- proteases that cleave ubiquitin chains or protein conjugates, are present in nearly every cellular compartment, with overlapping protein domain structure, localization, and functions. We discovered a cohort of DUBs that are involved in membrane trafficking (ubp4, ubp5, ubp9, ubp15, and sst2) and found that loss of all five of these DUBs but not loss of any combination of four, significantly impacted cell viability in the fission yeast Schizosaccharomyces pombe (1). Here, we delineate the collective and individual functions and activities of these five conserved DUBs using comparative proteomics, biochemistry, and microscopy. We find these five DUBs are degenerate rather than redundant at the levels of cell morphology, substrate selectivity, ubiquitin chain specificity, and cell viability under stress. These studies reveal the complexity of interplay among these enzymes, providing a foundation for understanding DUB biology and providing another example of how cells utilize degeneracy to improve survival.
authors.affiliation: From the Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232.
authors.forename: Janel R
authors.initials: JR
authors.lastname: Beckley
authors.affiliation: From the Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
authors.affiliation: From the Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232 kathy.gould@vanderbilt.edu.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gould
mesh_terms: D002462:Cell Membrane / Q000201:enzymology; D016764:Cell Polarity; D017124:Conserved Sequence; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D010450:Endopeptidases