Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity.
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Li, Jun, Tumanut, Christine, Gavigan, Julie-Ann, Huang, Waan, Hampton, Eric, Tuman, Rachelle, Suen, Ka Fai, Trauger, John, Spraggon, Glen, Lesley, Scott, Liau, Gene, Yowe, David and Harris, Jennifer (2007) Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. The Biochemical Journal, 406 (2). pp. 203-207. ISSN 1470-8728
Abstract
PCSK9 (proprotein convertase subtilisin/kexin 9) is a secreted serine protease that regulates cholesterol homoeostasis by inducing post-translational degradation of hepatic LDL-R [LDL (low-density lipoprotein) receptor]. Intramolecular autocatalytic processing of the PCSK9 zymogen in the endoplasmic reticulum results in a tightly associated complex between the prodomain and the catalytic domain. Although the autocatalytic processing event is required for proper secretion of PCSK9, the requirement of proteolytic activity in the regulation of LDL-R is currently unknown. Co-expression of the prodomain and the catalytic domain in trans allowed for production of a catalytically inactive secreted form of PCSK9. This catalytically inactive PCSK9 was characterized and shown to be functionally equivalent to the wild-type protein in lowering cellular LDL uptake and LDL-R levels. These findings suggest that, apart from autocatalytic processing, the protease activity of PCSK9 is not necessary for LDL-R regulation.
| Item Type: | Article |
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| Additional Information: | free final full text version available at publisher's official URL and at PubMedCentral; author can archive post-print (ie final draft post-refereeing); On author's personal web site or institutional repository |
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| Date Deposited: | 14 Dec 2009 14:05 |
| Last Modified: | 31 Jan 2013 01:27 |
| URI: | https://oak.novartis.com/id/eprint/115 |