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 UPS plays a central role in protein quality control, providing one of the primary routes by which the cell can remove potentially deleterious, aberrant and misfolded proteins, and maintain cellular protein homeostasis (Bhattacharyya et al., 2014; Buchberger et al., 2010; Komander and Rape, 2012; Wang and Terpstra, 2013; Wauer and Komander, 2014). A variety of effectors operate upstream of the UPS acting to recognise different classes of defective proteins and regulate their selective removal (Buchberger et al., 2010; Wang and Terpstra, 2013). Two such effectors are small glutamine-rich tetratricopeptide repeat containing protein alpha (SGTA) and the heterotrimeric BAG6 complex that, together, deal with polypeptide substrates that inappropriately expose hydrophobicity to the cytosol (Hessa et al., 2011; Leznicki and High, 2012; Minami et al., 2010; Rodrigo-Brenni et al., 2014; Wunderley et al., 2014). Hence, SGTA and the BAG6 complex are implicated in the quality control of mislocalised and secretory proteins, collectively termed mislocalised proteins (MLPs), which have failed to be correctly delivered to the endoplasmic reticulum (ER) and, consequently, become localised to the cytosol (Hessa et al., 2011; Leznicki and High, 2012; Rodrigo-Brenni et al., 2014; Wunderley et al., 2014).