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FEBS Letters
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FEBS Letters
Article . 2015 . Peer-reviewed
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FEBS Letters
Article . 2015
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MMP‐2 inhibits PCSK9‐induced degradation of the LDL receptor in Hepa1‐c1c7 cells

Authors: Wang, Xiang; Berry, Evan; Hernandez-Anzaldo, Samuel; Sun, Difei; Adijiang, Ayinuer; Li, Liang; Zhang, Dawei; +1 Authors

MMP‐2 inhibits PCSK9‐induced degradation of the LDL receptor in Hepa1‐c1c7 cells

Abstract

Low‐density lipoprotein receptor (LDLR) catalyzes the uptake of LDL‐cholesterol by liver and peripheral organs. The function of the LDLR is antagonized by pro‐protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the plasma membrane inducing LDLR degradation. Here, we report that matrix metalloproteinase‐2 (MMP‐2) interacts with and cleaves PCSK9, as evidenced by proteomic, chemical cross‐linkage, blue native‐PAGE and domain‐specific antibodies Western blot analyses. Furthermore, MMP‐2 overexpression renders Hepa1‐c1c7 cells resistant to PCSK9‐induced LDLR degradation. The data suggest that pathological MMP‐2 overexpression may protect the LDLR from PCSK‐9‐induced degradation.

Related Organizations
Keywords

Low density lipoprotein receptor, Molecular Sequence Data, Serine Endopeptidases, Pro-protein convertase subtilisin/kexin type 9, Atherosclerosis, Sterol-regulatory element binding protein, Cell Line, Mice, Cholesterol, Matrix metalloproteinase-2, Receptors, LDL, Proteolysis, Animals, Matrix Metalloproteinase 2, Amino Acid Sequence, Proprotein Convertases, Proprotein Convertase 9

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    13
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
13
Top 10%
Average
Top 10%
bronze