HRD1 in human malignant neoplasms: Molecular mechanisms and novel therapeutic strategy for cancer.

In tumor cells, the endoplasmic reticulum (ER) plays an essential role in maintaining cellular proteostasis by stimulating unfolded protein response (UPR) underlying stress conditions. ER-associated degradation (ERAD) is a critical pathway of the UPR to protect cells from ER stress-induced apoptosis and the elimination of unfolded or misfolded proteins by the ubiquitin-proteasome system (UPS). 3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) as an E3 ubiquitin ligase plays an essential role in the ubiquitination and dislocation of misfolded protein in ERAD.