Rad23 and Rpn10: perennial wallflowers join the melee

Substrate ubiquitination is highly regulated; by contrast, substrate targeting to the proteasome has been considered a stochastic process that is mediated primarily by high-affinity interaction with multi-ubiquitin chains. However, recent findings have shown that substrate recognition by the proteasome is also regulated, and requires Rad23, Dsk2 and Rpn10. These studies suggest that the engagement of protein ubiquitination and translocation with degradation by the proteasome is coordinated by a series of regulated events.