title: Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation.
abstract: The proprotein convertases subtilisin kexin 9 (PCSK9) binds to the epidermal growth factor domain A (EGF-A) of low-density lipoprotein receptor (LDLR) and leads to its destruction. However, the intracellular processes leading to LDLR degradation have not been fully delineated. In this report, we show that PCSK9 treatment can lead to ubiquitination of LDLR, which was enhanced in the presence of proteasome inhibitor MG132. Furthermore, LDLR protein carrying mutations in the C-terminal ubiquitination sites was resistant to PCSK9-mediated degradation. Our data suggest that the ubiquitination system is involved in PCSK9-induced LDLR degradation.
authors.affiliation: Department of Endocrine Research, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285, USA.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Chen
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.forename: Yue-Wei
authors.initials: YW
authors.lastname: Qian
authors.forename: Guoqing
authors.initials: G
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011973:Receptors, LDL / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D054875:Ubiquitination
chemical_list: D061988:Proteasome Inhibitors; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D046988:Proteasome Endopeptidase Complex