Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity.
Biochem J
; 406(2): 203-7, 2007 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-17608623
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, LDL
/
Serine Endopeptidases
Limits:
Humans
Language:
En
Journal:
Biochem J
Year:
2007
Document type:
Article
Affiliation country:
Estados Unidos