Binding of SGTA to Rpn13 selectively modulates protein quality control

Leznicki, Pawel; Korac-Prlic, Jelena; Kliza, Katarzyna; Husnjak, Koraljka; Nyathi, Yvonne; Dikic, Ivan; High, Stephen

The ubiquitin-proteasome system (UPS) constitutes a main pathway for protein degradation in eukaryotic cells, with polypeptides destined for disposal via this route bearing ubiquitin chains. The selective and covalent attachment of the small ubiquitin polypeptide to these proteins is typically through lysine residues within the substrates and occurs through a cascade of sequential reactions catalysed by E1, E2 and E3 enzymes (Komander and Rape, 2012). Furthermore, ubiquitin itself contains seven lysine residues, each of which can also serve as acceptor sites during ubiquitylation, leading to the formation of polyubiquitin chains with different linkages (Komander and Rape, 2012). Amongst these, K48- and K11-linked chains typically serve to hallmark proteins for proteasomal degradation (Komander and Rape, 2012). The 26S proteasome is a multiprotein complex composed of a 20S catalytic core where proteolysis occurs, and a 19S regulatory particle that controls substrate entry (Bhattacharyya et al., 2014; Komander and Rape, 2012). Protein ubiquitylation can be reversed by the action of proteases that are collectively known as deubiquitylating enzymes (DUBs) (Komander and Rape, 2012; Komander et al., 2009), and the removal of polyubiquitin by proteasomal DUBs precedes substrate degradation at the catalytic core (Bhattacharyya et al., 2014; Komander and Rape, 2012; Wauer and Komander, 2014).