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Variation in the human ApoB signal peptide modulates ApoB17 translocation

Benhizia, F; Ginsberg, HN; Humphries, SE; Talmud, PJ; (2001) Variation in the human ApoB signal peptide modulates ApoB17 translocation. BIOCHEM BIOPH RES CO , 283 (1) 149 - 157.

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Abstract

The functional effects of the common 27- or 24-amino-acid (aa) variants in the human apoB signal peptide (SP) on intracellular and secreted apoB17 were investigated in vitro. Only in the presence of oleate was a significant difference in intracellular and secreted SP27-B17 compared to SP24-B17 observed (P = 0.01 and P < 0.0007, respectively), although in the presence or absence of oleate mRNA levels from the two constructs were similar. After fractionation, oleate treatment enhanced microsomal SP27-B17 by 150% (P < 0.0005) with a modest but significant effect on SP24-B17 (32% P = 0.007). Oleate stimulated SP24-B17 accumulation in the nonmicrosomal fraction. The data suggest that the presence of oleate leads to inefficient translocation of the 24-amino-acid signal peptide, possibly resulting in increased retrograde translocation into the cytoplasm and reduced intracellular and secreted levels compared to the "wildtype" 27 aa SP. This implies a direct role of the SP variants in the regulation of apoB intracellular metabolism. (C) 2001 Academic Press.

Type:Article
Title:Variation in the human ApoB signal peptide modulates ApoB17 translocation
Keywords:apolipoprotein B, signal peptide variation, HUMAN APOLIPOPROTEIN-B, ENDOPLASMIC-RETICULUM MEMBRANE, LOW-DENSITY LIPOPROTEINS, INSERTION-DELETION POLYMORPHISM, UBIQUITIN-PROTEASOME PATHWAY, CARBOXYL-TERMINAL TRUNCATION, RAT HEPATOMA-CELLS, HEPG2 CELLS, INTRACELLULAR DEGRADATION, CHOLESTEROL LEVELS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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