A ubiquitin stress response induces altered proteasome composition.
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.
Hanna
John
J
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Meides
Alice
A
Zhang
Dan Phoebe
DP
Finley
Daniel
D
D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C109028:UBP6 protein, S cerevisiae