ER-associated degradation in protein quality control and cellular regulation

Abstract

The ER-associated degradation (ERAD) pathway directs ubiquitin-mediated degradation of a variety of ER-associated misfolded and normal proteins. Recent studies have delineated the molecular machinery responsible for protein ubiquitination and highlighted mechanistic questions surrounding the recognition, extraction and proteasomal destruction of the diverse array of ERAD substrates. Consideration of separate lines of work on this versatile pathway now indicate that despite its central role as an avenue of cellular quality control, ERAD is also harnessed for feedback regulation of sterol synthesis, and most likely numerous other cellular processes. These studies give ERAD a larger role in cellular function, and imply that cellular quality-control pathways could be widely employed in both natural and pharmaceutical control of individual proteins.