Selective degradation of an ER stress-induced protein by ER-associated degradation mechanism during stress recovery

Unfolded protein response (UPR) is a conserved signaling pathway that is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER) and stimulates production of ER chaperones to restore ER proteostasis. However, little is known how UPR-induced proteins return to their pre-stress levels upon removal of ER stress. TUNICAMYCIN-INDUCED1 (TIN1) is an Arabidopsis protein that is normally expressed in pollen but is rapidly induced by ER stresses in vegetative tissues. Here we show that the ER stress-induced TIN1 is rapidly degraded in the UPR recovery phase. We found that TIN1 degradation depends on its asparagine-linked glycans and requires both EMS-mutagenized bri1 suppressor 5 (EBS5) and EBS6 for its recruitment to the ER-associated degradation (ERAD) complex. Loss-of-function mutations in Arabidopsis ERAD components greatly stabilize TIN1. Interestingly, two other UPR-induced proteins that are coexpressed with TIN1 remained stable upon removal of ER stress, suggesting that rapid degradation during the stress-recovery phase likely applies to a subset of UPR-induced proteins. Further investigation should uncover the mechanisms by which the ERAD machinery differentially recognizes UPR-induced ER proteins.