Regulation of human apolipoprotein B gene expression at multiple levels.

Apolipoprotein B is a large, amphipathic protein that plays a central role in lipoprotein metabolism. Because its overproduction and deficiency leads to metabolic and pathologic disorders, much effort has been paid to investigate the mechanisms of how its homeostasis is achieved. Earlier and recent studies have showed that apoB gene locus might reside in different chromatin domains in the hepatic and intestinal cells, and two sets of very distinct regulatory elements operate to control its transcription. Posttranscriptional modification of apoB mRNA is performed by a multicomponent enzyme complex, several possible pathways regulate the editing efficiency. Understanding of the mechanism responsible for apoB mRNA editing will provide the basis for C-to-U editing in gene therapy. In addition to apoB mRNA abundance and stability, its translation can be also regulated at the steps of elongation. The translocation of apoB into the ER is an important and complicated process that is less understood. Successful transport and correct folding of apoB may lead to its final secretion, otherwise subject to intracellular degradation, which is accomplished by proteasomal and nonproteasomal pathways at multiple levels and may differ among cell types.