Regulating the 26S proteasome.

Despite the fact that the composition of proteasomes purified from different species is almost identical, and the basic components of the proteasome are remarkably conserved among all eukaryotes, there are quite a few additional proteins that show up in certain purifications or in certain screens. There is increasing evidence that the proteasome is in fact a dynamic structure forming multiple interactions with transiently associated subunits and cellular factors that are necessary for functions such as cellular localization, presentation of substrates, substrate-specific interactions, or generation of varied products. Harnessing the eukaryotic proteasome to its defined regulatory roles has been achieved by a number of means: (a) increasing the complexity of the proteasome by gene duplication, and differentiation of members within each gene family (namely the CP and RPT subunits); (b) addition of regulatory particles, complexes, and factors that influence both what enters and what exits the proteasome; and (c) signal-dependent alterations in subunit composition (for example, the CP beta to beta i exchange). It is not be surprising that the proteasome plays diverse roles, and that its specific functions can be fine-tuned depending on biological context or need.