CRISPR/Cas9 genome-wide screens using sterol-sensitive endogenous HMG-CoA reductase (HMGCR) reporter identify the sterol-responsive RNF145 and gp78 as independently responsible for sterol-accelerated degradation of HMGCR, the rate-limiting enzyme of cholesterol biosynthesis.
A deubiquitinase antagonizes the activity of an associated E3 ligase to prevent uncontrolled ubiquitination of a degradation machinery protein and thus maintain its functionality in protein quality control at the endoplasmic reticulum.
Attaching a molecule of adenosine mono-phosphate (AMP) to the BiP protein at threonine 518 regulates its chaperone activity in the endoplasmic reticulum.
Client protein-driven reversal of endoplasmic reticulum chaperone (BiP) mediated-repression is revealed as a principal component of the regulation of the unfolded protein response transducer IRE1 in cells.
Proinsulin misfolding, an established cause of diabetes in patients with INS gene mutations, is now observed in normal human pancreatic islets, and rodents with genetic predisposition to type 2 diabetes.
The extent of (proteotoxic) endoplasmic reticulum stress, and the ensuing unfolded protein response activation, are commensurate with the extent of the chaperone BiP being sequestered by its client proteins.
ER-resident chaperones and cargo receptors make excursions to the cell surface and endocytic compartments when they accompany misfolded clients to lysosomes for degradation.
The co-chaperone CHORDC1 is specifically required for epidermal growth factor receptor trafficking and signaling in Caenorhabditis elegans and in human cells.
Activation of the integrated stress response by stalled translation elongation complexes attenuates neurodegeneration, and demonstrates a protective link between a decrease in the rate of translation initiation and defects in translation elongation.
