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Proprotein convertase subtilisin/kexin type 9 inhibits interferon β expression through interacting with ATF ‐2
Author(s) -
Li Zhubing,
Liu Qiang
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13152
Subject(s) - proprotein convertase , kexin , pcsk9 , subtilisin , enhancer , chemistry , transcription factor , transcription (linguistics) , biology , microbiology and biotechnology , ldl receptor , biochemistry , gene , lipoprotein , enzyme , cholesterol , linguistics , philosophy
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.