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APOB — PCSK9
Text-mined interactions from Literome
Maxwell et al., Proc Natl Acad Sci U S A 2004
:
These results were confirmed in vitro by the demonstration that transfection of
Pcsk9 in McA-RH7777 cells
caused a reduction in LDLR protein and
LDL binding
Maxwell et al., Proc Natl Acad Sci U S A 2005
:
Overexpression of
PCSK9 in mice
leads to increased total and
low-density lipoprotein (LDL) cholesterol levels because of a decrease in hepatic LDL receptor (LDLR) protein with normal mRNA levels
Sun et al., Hum Mol Genet 2005
(Carcinoma, Hepatocellular...) :
Evidence for
effect of mutant
PCSK9 on
apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia
Soutar et al., Nat Clin Pract Cardiovasc Med 2007
(Genetic Predisposition to Disease...) :
Expression of
PCSK9 normally downregulates the LDL-receptor pathway by indirectly causing degradation of LDL-receptor protein, and loss-of-function mutations in PCSK9
result in low plasma
LDL levels
Cunningham et al., Nature structural & molecular biology 2007
(Hypercholesterolemia) :
PCSK9 may
diminish LDL receptors by a mechanism that requires direct binding but not necessarily receptor proteolysis
Fisher et al., J Biol Chem 2007
(Genetic Diseases, Inborn...) :
Although
PCSK9 controls
low density lipoprotein (LDL) receptor ( LDLR ) levels post-transcriptionally, several questions concerning its mode of action remain unanswered ... Finally, we show that
LDL diminishes
PCSK9 binding to LDLR in vitro and partially inhibits the effects of secreted PCSK9 on LDLR degradation in cell culture
Grefhorst et al., J Lipid Res 2008
:
Plasma
PCSK9 preferentially
reduces liver
LDL receptors in mice
Frank-Kamenetsky et al., Proc Natl Acad Sci U S A 2008
:
Loss of
PCSK9 increases LDLR levels in liver and
reduces plasma
LDL cholesterol (LDLc) , whereas excess PCSK9 activity decreases liver LDLR levels and increases plasma LDLc
Hedrick et al., Curr Opin Investig Drugs 2009
(Hypercholesterolemia) :
PCSK9 ( proprotein convertase subtilisin/kexin type 9 )
mediates the post-translational degradation of the
LDL receptor (LDLR) and, as a result, modulates serum levels of LDL-cholesterol (LDL-C)
Strøm et al., Clin Chim Acta 2010
(Hyperlipoproteinemia Type II) :
Thus, in the
presence of high
LDL levels,
wild-type-PCSK9 , which has twice the binding affinity of R46L-PCSK9 to bind to the LDLR, may not be significantly more potent in degrading the LDLR than R46L-PCSK9
Wu et al., Mol Cell Biochem 2012
:
This paper investigated the
effects of
ox-LDL on
PCSK9 , and the molecular mechanisms of PCSK9 siRNA inhibited apoptosis induced by ox-LDL in human umbilical vein endothelial cells ( HUVECs ), to clarify the role of PCSK9 in atherosclerogenesis ... However,
ox-LDL induced HUVEC apoptosis and
PCSK9 expression, but not LOX-1 expression, were significantly reduced by PCSK9 siRNA
Ai et al., J Clin Invest 2012
(Hyperinsulinism...) :
Regulation of hepatic
LDL receptors by mTORC1 and
PCSK9 in mice
Saavedra et al., J Biol Chem 2012
:
PCSK9 enhances the cellular degradation of the
LDL receptor (LDLR) , leading to increased plasma LDL cholesterol
Kosenko et al., J Biol Chem 2013
:
LDL also
inhibited PCSK9 binding to mutant LDLRs defective at binding LDL