Getting in and out of the proteasome

By far the best understood role of the proteasome is to remove ubiquitin-conjugated proteins from eukaryotric cells by hydrolysing them into small peptides of varying lengths. These include both misfolded/abnormal proteins, as well as 'normal' proteins that need to be rapidly removed for regulatory purposes. However, the proteasome is also present in numerous prokaryotic organisms, while ubiquitin, and the ubiquitin conjugating system, are not. The eukaryotic proteasome has been adapted to degrading proteins in a ubiquitin-dependent fashion by the addition of regulatory factors that assemble in different layers onto the proteolytic core of the proteasome, and by increasing the diversity of the core subunits as well. In addition to hydrolysing ubiquitinated proteins into amino acids, the proteasome can also proteolyse selected non-ubiquitinated proteins, process proteins, and possibly refold misfolded proteins. This review will focus on the different proteasome functions, and how these are used in the multiple regulatory roles the proteasome plays in eukaryotic cells.