Biological process

endoplasmic reticulum-associated degradation, protein degradation by ERAD

The protein catabolic pathway which targets endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. It begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein modifications necessary for correct substrate transfer (e.g. ubiquitination), transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome.

ER-associated degradation pathway, endoplasmic reticulum-associated protein degradation pathway

ER-associated protein degradation (ERAD) pathways target misfolded ER lumenal proteins (ERAD-L), ER membrane proteins (ERAD-M), and ER proteins with misfolded cytosolic domains (ERAD-C) by recognizing aberrant proteins, retrotranslocating these substrates to the cytosol, followed by substrate ubiquitination and proteosomal-mediated degradation. In contrast the stress-induced homeostatically regulated protein degradation (SHRED) pathway (GO:0120174), although inducible by stress, targets diverse ER membrane, and cytosolic proteins as well as numerous other native proteins in the absence of stress. Stress results in the protease-mediated (Nma111p) generation of a Roq1p cleavage product that then binds to the type-1 active site of Ubr1p, altering its substrate specificity, and leading to the proteasome-mediated degradation of both misfolded and native proteins. Although the SHRED pathway may contain some components in common with ERAD pathways (GO:0036503), such as UBR1, RAD6 and CDC48, other ERAD components, such as HRD1 and DOA10, do not appear to be involved, and as such these pathways are currently considered to be distinct.