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Direct and essential function for Hrd3 in ER-associated degradation.

Proc. Natl. Acad. Sci. U.S.A.. 2016; 
VashisthaNidhi,NealSonya E,SinghAmanjot,CarrollSarah M,HamptonRandol
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摘要

The HRD (HMG-CoA reductase degradation) pathway is a conserved route of endoplasmic reticulum-associated degradation (ERAD), by which misfolded ER proteins are ubiquitinated and degraded. ERAD substrates are ubiquitinated by the action of the Hrd1 RING-H2 E3 ligase. Hrd1 is always present in a stoichiometric complex with the ER membrane protein Hrd3, which is also required for HRD-dependent degradation. Despite its conserved presence, unequivocal study of Hrd3 function has been precluded by its central role in Hrd1 stability. Loss of Hrd3 causes unrestricted self-degradation of Hrd1, resulting in significant loss of the core ligase. Accordingly, the degree to which Hrd3 functions independently of Hrd1... More

关键词

ERAD,HRD pathway,HRD3,quality control,ubiqu