Regulatory subunit interactions of the 26S proteasome, a complex problem

The 26S proteasome is the major non-lysosomal protease in eukaryotic cells. This multimeric enzyme is the integral component of the ubiquitin-mediated substrate degradation pathway. It Consists of two subcomplexes, the 20S pr oteasome, which forms the proteolytic core, and the 19S regulator (or PA700 ), which confers ATP dependency and ubiquitinated substrate specificity on the enzyme. Recent biochemical and genetic studies have revealed many of th e interactions between the 17 regulatory subunits, yielding an approximatio n of the 19S complex topology. Inspection of interactions of regulatory sub units with non-subunit proteins reveals patterns that suggest these interac tions play a role in 26S proteasome regulation and localization.