Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1.
J Lipid Res
; 50(7): 1330-9, 2009 Jul.
Article
em En
| MEDLINE
| ID: mdl-19237735
ABSTRACT
Given the increased prevalence of cardiovascular disease in the world, the search for genetic variations controlling the levels of risk factors associated with the development of the disease continues. Multiple genetic association studies suggest the involvement of procollagen C-proteinase enhancer-2 (PCPE2) in modulating HDL-C levels. Therefore biochemical and mechanistic studies were undertaken to determine whether there might be a basis for a role of PCPE2 in HDL biogenesis. Our studies indicate that PCPE2 accelerates the proteolytic processing of pro-apolipoprotein (apo) AI by enhancing the cleavage of the hexapeptide extension present at the N terminus of apoAI. Surface Plasmon Resonance and immunoprecipitation studies indicate that PCPE2 interacts with BMP-1 and pro-apoAI to form a ternary pro-apoAI/BMP-1/PCPE2 complex. The most favorable interaction among these proteins begins with the association of BMP-1 to pro-apoAI followed by the binding of PCPE2 which further stabilizes the complex. PCPE2 resides, along with apoAI, on the HDL fraction of lipoproteins in human plasma supporting a relationship between HDL and PCPE2. Taken together, the findings from our studies identify a new player in the regulation of apoAI post-translational processing and open a new avenue to the study of mechanisms involved in the regulation of apoAI synthesis, HDL levels, and potentially, cardiovascular disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Precursores de Proteínas
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Glicoproteínas
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Proteínas da Matriz Extracelular
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Apolipoproteína A-I
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Proteína Morfogenética Óssea 1
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos