Apolipoprotein B mRNA editing protein: a tool for dissecting lipoprotein metabolism and a potential therapeutic gene for hypercholesterolemia.

Apolipoprotein (apo) B mRNA editing protein is an essential catalytic component of the apoB mRNA editing enzyme complex. Its cDNA has been cloned recently from rats and humans. In the presence of other proteins of the editing enzyme complex, it will deaminate nucleotide 6666 in apoB mRNA, a cytidine residue, converting it to uridine. The end result of this reaction is the production of apoB-48 in place of apoB-100. The editing protein exists as a homodimer. It imparts editing activity to HepG2, a human hepatoma cell line, causing these cells to start producing apoB-48 in addition to apoB-100. Therefore, it can be used as a therapeutic agent to reduce apoB-100 production. Preliminary experiments in our laboratory indicate that somatic gene transfer of the editing protein is highly effective in lowering plasma low density lipoproteins.