Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
-
Alexander Y. Amerik
Abstract
Attachment of proteins to ubiquitin is reversed by specialized proteases called deubiquitinating enzymes (Dubs), which are also essential for ubiquitin precursor processing. In the genome of Saccharomyces cerevisiae, 17 potential DUB genes can be discerned. We have now constructed strains deleted for each of these genes. Surprisingly, given the essential nature of the ubiquitin system, none of the mutants is lethal or strongly growth defective under standard conditions, although a number have detectable abnormalities. Including results from this study, 14 of the 17 Dubs have now been shown to have ubiquitin-cleaving activity. The most extensively characterized yeast Dub is Doa4, which is required for both ubiquitin homeostasis and proteasome-dependent proteolysis. To help determine what distinguishes Doa4 functionally from other Dubs, we have cloned a DOA4 ortholog from the yeast Kluyveromyces lactis. The K. lactis protein is 42% identical to Doa4, but unexpectedly the K. lactis gene is slightly closer in nucleotide sequence to UBP5, which cannot substitute for DOA4 even in high dosage. The data suggest that the DOA4 locus underwent a duplication after the divergence of K. lactis and S. cerevisiae. This information will facilitate fine-structure analysis of the Doa4 protein to help delineate its key functional elements.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Alexander J. Varshavsky Felix Hoppe-Seyler Lecturer 2000
- The Ubiquitin System and the N-End Rule Pathway
- Paper of the Year 1999: Award to Igor Stagljar
- A Clockwork Organ
- The Transgeneticists Toolbox: Novel Methods for the Targeted Modification of Eukaryotic Genomes
- Interdependence of Filamentous Actin and Microtubules for Asymmetric Cell Division
- Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
- Phosphorylcholine Substituents in Nematodes: Structures, Occurrence and Biological Implications
- Selenium in Biology: Facts and Medical Perspectives
- The Role of Se, Mo and Fe in the Structure and Function of Carbon Monoxide Dehydrogenase
- Molecular Basis for Interactions of the DnaK Chaperone with Substrates
- Protein Import: the Hitchhikers Guide into Chloroplasts
- Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum
- Metabolic Networks: a Signal-Oriented Approach to Cellular Models
- Representing and Analysing Molecular and Cellular Function Using the Computer
- Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- The Mitochondrial Protein Import Motor
- The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach
- Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
- Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
- Macromolecular Intelligence in Microorganisms
- Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter
- Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
- Helical Tubes of FtsZ from Methanococcus jannaschii
- Surface Topography of Microtubule Walls Decorated with Monomeric and Dimeric Kinesin Constructs
- Histone Deacetylase Activity Is Required for the Induction of the MyoD Muscle Cell Lineage in Xenopus
- The Effect of Heat Shock on 20S/26S Proteasomes
- Sec61p Is the Main Ribosome Receptor in the Endoplasmic Reticulum of Saccharomyces cerevisiae
Articles in the same Issue
- Alexander J. Varshavsky Felix Hoppe-Seyler Lecturer 2000
- The Ubiquitin System and the N-End Rule Pathway
- Paper of the Year 1999: Award to Igor Stagljar
- A Clockwork Organ
- The Transgeneticists Toolbox: Novel Methods for the Targeted Modification of Eukaryotic Genomes
- Interdependence of Filamentous Actin and Microtubules for Asymmetric Cell Division
- Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
- Phosphorylcholine Substituents in Nematodes: Structures, Occurrence and Biological Implications
- Selenium in Biology: Facts and Medical Perspectives
- The Role of Se, Mo and Fe in the Structure and Function of Carbon Monoxide Dehydrogenase
- Molecular Basis for Interactions of the DnaK Chaperone with Substrates
- Protein Import: the Hitchhikers Guide into Chloroplasts
- Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum
- Metabolic Networks: a Signal-Oriented Approach to Cellular Models
- Representing and Analysing Molecular and Cellular Function Using the Computer
- Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- The Mitochondrial Protein Import Motor
- The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach
- Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
- Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
- Macromolecular Intelligence in Microorganisms
- Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter
- Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
- Helical Tubes of FtsZ from Methanococcus jannaschii
- Surface Topography of Microtubule Walls Decorated with Monomeric and Dimeric Kinesin Constructs
- Histone Deacetylase Activity Is Required for the Induction of the MyoD Muscle Cell Lineage in Xenopus
- The Effect of Heat Shock on 20S/26S Proteasomes
- Sec61p Is the Main Ribosome Receptor in the Endoplasmic Reticulum of Saccharomyces cerevisiae