Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels

Francone, Omar L.; Ishida, Brian Y.; Llera-Moya, Margarita de la; Royer, Lori; Happe, Christiane; Zhu, Jian; Chalkey, Robert J.; Schaefer, Peter M.; Cox, Cheryl J.; Burlingame, Alma L.; Kane, John P.; Rothblat, George H.

doi:10.1194/jlr.m016527

Cited by 24 publications

(32 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Suggestive but inconclusive genetic studies have implicated PCPE2 in modulating serum levels of HDL, whereas biochemical studies have shown PCPE2 to be associated with serum HDL and to be capable of binding both pro-ApoA1 and BMP1 and perhaps enhancing proApoA1 processing by BMP1 in vitro (88). In vivo roles for PCPE2 in modulating HDL levels and pro-ApoA1 processing are supported by recent findings of decreased pro-ApoA1 processing and changes to HDL levels and properties in PCPE2-null mice (89). PCPE1 is also found in serum, and differential glycosylation of serum PCPE1 has been reported as a potential marker for levels of collagen remodeling in humans (90).…”

Section: Pcp Enhancersmentioning

confidence: 53%

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

Muir

Greenspan

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Many secreted proteins are synthesized as precursors with propeptides that must be cleaved to yield the mature functional form of the molecule. In addition, various growth factors occur in extracellular latent complexes with protein antagonists and are activated upon cleavage of such antagonists. Research in the separate fields of embryonic patterning and extracellular matrix formation has identified members of the BMP1/Tolloid-like family of metalloproteinases as key players in these types of biosynthetic processing events in species ranging from Drosophila to humans. Bone morphogenic proteins (BMPs)2 were first defined by the ability to induce de novo bone formation and were first identified in bone extracts (1). Although all other BMPs are members of the TGF␤ superfamily of growth factors, BMP1 is a metalloproteinase, the first demonstrated role of which was as a procollagen C-proteinase (pCP) (2) that cleaves C-propeptides from procollagen precursors to produce mature monomers of the major fibrillar collagens I-III. This activity is crucial to bone biology, as collagen I is the major protein component of bone and is essential to bone structure/function. After initial cloning of mammalian BMP1, Tolloid (TLD), the protein product of a zygotically active gene involved in dorsoventral patterning of Drosophila embryos, was shown to have a domain structure resembling that of BMP1 (3) and was later shown to exert patterning effects by activating the TGF␤-like BMP decapentaplegic (DPP) (4). Subsequently, BMP1 and TLD have become prototypes of the BMP1/TLD-like proteinase (B/TP) family. B/TPs in a broad range of species are now implicated in processes that include extracellular matrix (ECM) formation and mineralization, embryonic patterning, growth factor activation, and generation of anti-angiogenic protein fragments, all via cleavage of a growing list of substrates.

show abstract

Section: Pcp Enhancersmentioning

confidence: 53%

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

Muir

Greenspan

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The Absence of PCPE2 Affects Lipoprotein Distribution and Concentration-PCPE2-deficient mice in the C57BL/6 background (43) were characterized with respect to HDL size and concentration for comparison with the previously published phenotype (44). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…PCPE2 knock-out mice had elevated concentrations of enlarged plasma HDL (44), despite displaying defective ABCA1-mediated cholesterol efflux capacity. Thus, reduced cholesterol efflux is paradoxically associated with elevated plasma HDL cholesterol in PCPE2-deficient mice.…”

mentioning

confidence: 97%

Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake

Pollard

Blesso

Zabalawi

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Extracellular matrix protein PCPE2 is linked to alterations in HDL size and concentration. Results: PCPE2 protects against diet-induced atherosclerosis by promoting HDL catabolism, reverse cholesterol transport, and SR-BI-mediated uptake of HDL-cholesteryl ester. Conclusion: PCPE2 mediates HDL function by reducing lipid and immune cell accumulation in the artery. Significance: These findings establish a role for the extracellular matrix glycoprotein PCPE2 in SR-BI-mediated HDL function and the prevention of atherosclerosis.

show abstract

“…The bone morphogenetic protein-1 has been identified as enzyme that cleaves human apolipoprotein A-I [21]. The procollagen C-proteinase enhancer is involved in the proteolytic processing of proapoA-I [22]. Several possible functions of the propeptide extension have been discussed.…”

Section: /Mgmentioning

confidence: 99%

Feedback inhibition of apolipoprotein A-I synthesis by its propeptide in hepatocyte cell culture and in the cell-free system

Weigand¹,

Tischler-David²,

Gebhardt³

et al. 2017

J Hepatol Gastroenterol.

View full text Add to dashboard Cite

Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels

Cited by 24 publications

References 41 publications

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes

Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake

Feedback inhibition of apolipoprotein A-I synthesis by its propeptide in hepatocyte cell culture and in the cell-free system

Contact Info

Product

Resources

About