Identification of protein disulfide isomerase 1 as a key isomerase for disulfide bond formation in apolipoprotein B100.
Bottom Line: Although these disulfide bonds were suggested to be important in maintaining apoB100 function, neither the specific oxidoreductase involved nor the direct role of these disulfide bonds in apoB100-lipidation is known.Here we used RNA knockdown to evaluate both MTP-dependent and -independent roles of PDI1 in apoB100 synthesis and lipidation in McA-RH7777 cells.Further, we demonstrate that PDI1 directly interacts with apoB100 via its redox-active CXXC motifs and assists in the oxidative folding of apoB100.
Affiliation: Degenerative Diseases Research Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.Show MeSH
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Mentions: We next examined protein levels of apoB100 and MTP and found that Pdi1 knockdown drastically decreased intracellular apoB100 levels by ∼50% without altering its mRNA expression. Pdi1 knockdown had a relatively milder effect on MTP, with a ∼20% decrease in steady-state protein levels (Figure 2, A and B). Nonetheless, these observations indicate that PDI1 plays an essential role in maintaining intracellular apoB100 levels.
Affiliation: Degenerative Diseases Research Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.