Mammalian proteasome subtypes: Their diversity in structure and function

•The 20S Proteasome is the proteolytically active centre of the ubiquitin-proteasome system.•20S proteasomes are subdivided into standard-, immuno-, and intermediate-proteasome subpopulations.•Each 20S proteasome subunit exists in several proteoforms.•20S proteasome subtypes are composed of different subunit proteoforms.

The 20S proteasome is a multicatalytic proteinase catalysing the degradation of the majority of intracellular proteins. Thereby it is involved in almost all basic cellular processes, which is facilitated by its association with various regulator complexes so that it appears in different disguises like 26S proteasome, hybrid-proteasome and others. The 20S proteasome has a cylindrical structure built up by four stacked rings composed of α- and β-subunits. Since the three active site-containing β-subunits can all or in part be replaced by immuno-subunits, three main subpopulations exist, namely standard-, immuno- and intermediate-proteasomes. Due to posttranslational modifications or/and genetic variations all α- and β-subunits occur in multiple iso- or proteoforms. This leads to the fact that each of the three subpopulations is composed of a variety of 20S proteasome subtypes. This review summarizes the knowledge of proteasome subtypes in mammalian cells and tissues and their possible biological and medical relevancy.