Proteolysis by the 26S Proteasome

PA700/19S RP has been studied in many different species, and many individual subunits were identified prior to realization that they were components of PA700. These factors have resulted in a diverse and confusing subunit nomenclature (Table 11.1). The rational and increasingly accepted Rpt/Rpn and S nomenclatures (see below) will be used in the current presentation. An introductory description of PA700/19S PR subunits follows immediately below. Additional details of subunit functions and regulatory features in proteolysis by the 26S proteasome are presented in later sections. 

The 26S proteasome also degrades non-ubiquitylated proteins [71]. The short-lived enzyme ornithine decarboxylase (ODC) and the cell-cycle regulator p21Cip provide well documented examples of ubiquitin-independent proteolysis by the 26S en-... 

The degradation of ubiquitinated proteins by the 26S proteasome requires PA700-catalyzed ATP hydrolysis. How is proteolysis mechanistically linked to ATPase activity Despite the fundamental nature of this question, a detailed answer is unknown. As described below, ATP hydrolysis probably mediates multiple elements... 

It forms supercomplexes consisting of both the ubiquitinating and the proteolytic machineries. According to this model, the substrate first binds to the CSN, is then ubiquitinated by the associated Ub ligase and finally directly charmeled into the 26S proteasome. Deneddylation, deubiquitination and phosphorylation are necessary to maintain the supercomplex, to protect the intermediates and to stimulate proteolysis. 

---