Induction of ER stress by variants of the prohormone convertase 1 (PCSK1)-gene

Background & Hypotheses: Prohormone convertase 1 encoded by the PCSK1 gene processes and activates multiple prohormones such as proinsulin in the pancreas. Some variants within this gene are associated with polygenic obesity and rare mutations cause childhood obesity and abnormal glucose homeostasis. The unfolded protein response (UPR) is a cellular mechanism protecting the cell against the effects of an accumulation of falsely folded proteins in the endoplasmic reticulum (ER). A continuously activated UPR leads to apoptosis. We hypothesized that variants of PCSK1 can lead to falsely folded proteins and subseque…