Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation.
Ubiquitin chains serve as a recognition motif for the proteasome, a multisubunit protease, which degrades its substrates into polypeptides while releasing ubiquitin for reuse. Yeast proteasomes contain two deubiquitinating enzymes, Ubp6 and Rpn11. Rpn11 promotes protein breakdown through its degradation-coupled activity. In contrast, we show here that Ubp6 has the capacity to delay the degradation of ubiquitinated proteins by the proteasome. However, delay of degradation by Ubp6 does not require its catalytic activity, indicating that Ubp6 has both deubiquitinating activity and proteasome-inhibitory activity. Delay of degradation by Ubp6 appears to provide a time window allowing gradual deubiquitination of the substrate by Ubp6. Rpn11 catalyzes en bloc chain removal, and Ubp6 interferes with degradation at or upstream of this step, so that degradation delay by Ubp6 is accompanied by a switch in the mode of ubiquitin chain processing. We propose that Ubp6 regulates both the nature and magnitude of proteasome activity.
Hanna
John
J
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Hathaway
Nathaniel A
NA
Tone
Yoshiko
Y
Crosas
Bernat
B
Elsasser
Suzanne
S
Kirkpatrick
Donald S
DS
Leggett
David S
DS
Gygi
Steven P
SP
King
Randall W
RW
Finley
Daniel
D
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism; D003513:Cycloheximide / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000302:isolation & purification / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D019926:Cyclin B; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011500:Protein Synthesis Inhibitors; C115451:RPN11 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D003513:Cycloheximide; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C109028:UBP6 protein, S cerevisiae; C078846:epoxomicin