A ubiquitin stress response induces altered proteasome composition. 2007

John Hanna, and Alice Meides, and Dan Phoebe Zhang, and Daniel Finley
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Ubiquitin-dependent protein degradation is essential for cells to survive many environmental stresses. Thus, it may be necessary to buffer ubiquitin and proteasome pools against fluctuation. Proteasome levels are tightly regulated, and proteasome deficiency stimulates a stress response. Here we report a novel pathway of cellular response to ubiquitin depletion. Unlike proteasome stress, ubiquitin stress does not upregulate proteasome abundance. Instead, ubiquitin stress alters proteasome composition. The proteasome-associated deubiquitinating enzyme Ubp6, which spares ubiquitin from proteasomal degradation, is induced by ubiquitin deficiency. This enhances loading of proteasomes with Ubp6, thereby altering proteasome function. A catalytically inactive mutant of Ubp6 fails to recycle ubiquitin and also inhibits proteasome function directly, thus inducing both ubiquitin stress and proteasome stress. These results show that homeostatic control of the ubiquitin-proteasome pathway can be achieved through signal-dependent, subunit-specific regulation of the proteasome, and indicate a dual role of Ubp6 in regulating ubiquitin levels and proteasome function.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D015966 Gene Expression Regulation, Fungal Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi. Fungal Gene Expression Regulation,Regulation of Gene Expression, Fungal,Regulation, Gene Expression, Fungal
D046988 Proteasome Endopeptidase Complex A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme. 20S Proteasome,Ingensin,Macropain,Macroxyproteinase,Multicatalytic Endopeptidase Complex,Multicatalytic Proteinase,Prosome,Proteasome,Complex, Multicatalytic Endopeptidase,Complex, Proteasome Endopeptidase,Endopeptidase Complex, Multicatalytic,Endopeptidase Complex, Proteasome,Proteasome, 20S,Proteinase, Multicatalytic
D025801 Ubiquitin A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell. APF-1,ATP-Dependent Proteolysis Factor 1,HMG-20,High Mobility Protein 20,Ubiquitin, Human,ATP Dependent Proteolysis Factor 1,Human Ubiquitin
D029701 Saccharomyces cerevisiae Proteins Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. Baker's Yeast Proteins,S cerevisiae Proteins

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