T he ubiquitin-proteasome pathway is a major mediator of posttranslational control in eukaryotes, which functions in the control of cell proliferation, the cell cycle, and other processes. Conjugation of ubiquitin to substrates such as cyclins and p 5 3 target them for degradation by the proteasome. The proteasome holoenzyme can be dissociated in vitro into a core particle (CP) and a regulatory particle (RP; the RP is also referred to as the 19S complex or PA700 in mammals, and the m particle in D. melanogaster}) In S. cerevisiae, the CP contains 14 subunits, and the RP at least 18 (see ref. 2 and references therein).