The traditional view of the proteasome was, says Finley, “like a pencil sharpener,” mindlessly chewing away at ubiquitinated proteins. The characterization of one proteasome-associated factor now changes that view. Ubp6, the team shows, actually delays the rate of protein destruction. Proteasomes purified from yeast Ubp6 deletion mutants degraded ubiquitinated cyclin B protein faster than did those from their wild-type counterparts.
Ubp6 is a deubiquitinase, but this activity was not responsible for delaying degradation. Inhibiting its deubiquitinase active site did not speed up degradation. Ubp6 also needed to be bound to the proteasome to delay degradation, which would not be necessary if the delay tactic was simply to prevent targeting of proteins to the proteasome by removing ubiquitin moieties.
Instead, Ubp6 seems to delay degradation, at least in part, by inhibiting the action of a second proteasome component, called Rpn11. Rpn11 is itself a deubiquitinase whose activity is strictly coupled with degradation, unlike Ubp6.
Though Rpn11 inhibition might not be the sole cause for the degradation delay, it is clear that the proteasome is a more finely self-tuning machine than was first thought.