[HTML][HTML] Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained
P Lebeau, K Platko, AA Al-Hashimi, JH Byun… - Journal of Biological …, 2018 - ASBMB
The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in
cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor
(LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic
reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD. The
retention of misfolded protein in the ER can cause ER stress and activate the unfolded
protein response (UPR). In this study, we investigated whether a variety of LOF PCSK9 …
cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor
(LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic
reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD. The
retention of misfolded protein in the ER can cause ER stress and activate the unfolded
protein response (UPR). In this study, we investigated whether a variety of LOF PCSK9 …