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Publication : MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.

First Author  Wang X Year  2015
Journal  FEBS Lett Volume  589
Issue  4 Pages  490-6
PubMed ID  25613181 Mgi Jnum  J:217653
Mgi Id  MGI:5615289 Doi  10.1016/j.febslet.2015.01.007
Citation  Wang X, et al. (2015) MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells. FEBS Lett 589(4):490-6
abstractText  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.
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