Proprotein convertase subtilisin/kexin type 9 inhibits interferon β expression through interacting with ATF ‐2

Proprotein convertase subtilisin/kexin type 9 ( PCSK 9) regulates lipid metabolism. A mutual interplay of lipid homeostasis and innate immune system has been increasingly recognized. We, therefore, studied the effect of PCSK 9 on interferon ( IFN ) β expression. We show that PCSK 9 decreases IFN β promoter/enhancer activity, mRNA and protein levels, and its downstream 2′,5′‐oligoadenylate synthetase‐1 mRNA level. Pro PCSK 9, but not the cleaved PCSK 9, down‐regulates IFN β promoter/enhancer activity. Moreover, PCSK 9 decreases IFN β promoter/enhancer activity through the positive regulatory domain IV region where the activating transcription factor‐2 ( ATF ‐2)/c‐Jun heterodimer binds. Mechanistically, we demonstrate an interaction between PCSK 9 and ATF ‐2, which reduces ATF ‐2/c‐Jun dimerization and ATF ‐2/c‐Jun binding to the IFN β enhancer. This novel function of PCSK 9 should have important implications in optimizing the clinical use of PCSK 9 inhibitors.