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

Hydrophobic MLPs enter a cytosolic quality control pathway that appears to be mediated by the coordinated activity of the BAG6 complex and SGTA (Hessa et al., 2011; Leznicki and High, 2012). Hence, BAG6 promotes the RNF126-dependent ubiquitylation and proteasomal degradation of MLPs (Hessa et al., 2011; Rodrigo-Brenni et al., 2014), whereas SGTA acts to delay their degradation and promotes the accumulation of deubiquitylated MLPs (Leznicki and High, 2012; Wunderley et al., 2014). We now show that SGTA is selectively recruited to the proteasome through Rpn13, and provide evidence that this interaction may regulate MLP stability. Using yeast two-hybrid and biochemical approaches, we identify a direct physical interaction between the TPR region of SGTA and the C-terminal region of Rpn13. Treatment with MG132 results in a fraction of endogenous SGTA becoming stably associated with the proteasome, consistent with our proposal that these components interact in a cellular context.