Degradation or Maintenance: Actions of the Ubiquitin System on Eukaryotic Chromatin

Regulation of gene expression by transcriptional repression or activation has long been recognized as an effective means to control a biological process. However, while the initiation of an event can be governed by turning on the gene encoding a key rate-limiting enzyme mediating the respective action, its ter- mination must often be equally tightly controlled by inactivat- ing the responsible factor. Complete destruction is possibly the most effective way of ensuring the irreversible inactivation of a protein; consequently, all organisms employ intracellular pro- teolytic systems for the selective removal of "unwanted" pro- teins. This category includes short-lived regulatory factors as well as proteins that have been damaged or incapacitated by heat or other types of stress or toxic agents. In eukaryotes, regulated proteolysis is mediated largely by the 26S protea- some, a multicatalytic protease that consists of a barrel-shaped proteolytic 20S core particle in association with a 19S cap complex (20, 126). In contrast to a large portion of bulk protein turnover, which is mediated by vacuolar or lysosomal pro- teases, proteolysis by the 26S proteasome is energy dependent, due to the presence of ATPases of the AAA type within the 19S cap, which are responsible for unfolding the target pro-