Fig. 9
From: PRKCSH contributes to tumorigenesis by selective boosting of IRE1 signaling pathway
A proposed model for the dual function of PRKCSH in ER protein quality control. Under resting conditions, PRKCSH functions as the noncatalytic beta subunit of glucosidase II, which catalyzes glucose trimming from newly synthesized glycoproteins and ensures secretion of properly folded glycoproteins and targeting improperly folded glycoproteins for degradation by the ERAD pathway. This is mediated by the interaction of PRKCSH with glucosidase II alpha subunit (GIIα) through the G2B domain and with mannose residues of glycoproteins through the MRH domain of PRKCSH. Under ER stress, PRKCSH dissociates from the GIIα subunit and subsequently associates with IRE1α through its internal E/P domain, which leads to autophosphorylation and oligomerization of IRE1α followed by RNase-mediated splicing of XBP1 and kinase domain-mediated phosphorylation of MAPKs, thereby selectively promoting activation of the IRE1α signaling branch. Findings from this study are shown on a yellow background, whereas the known function of PRKCSH is shown on a white background
