Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathway.

Co- and posttranslational regulation of apolipoprotein B (apoB) has been postulated to involve degradation by both proteasomal and nonproteasomal pathways; however, nonproteasomal mechanisms of apoB degradation are currently unknown. We have previously demonstrated an intracellular association of newly synthesized apoB with endoplasmic reticulum (ER)-60, an ER-localized protein, possessing both proteolytic and chaperone activities. In the present paper, adenoviral expression vectors containing rat ER-60 cDNA were used to achieve dose- and time-dependent overexpression of ER-60 to investigate its role in apoB100 turnover.

Insulin regulates hepatic apolipoprotein B production independent of the mass or activity of Akt1/PKBalpha.

Insulin is known to be a downregulator of apolipoprotein B (apoB) via the phosphatidylinositol 3-kinase (PI3K) pathway. Akt, also known as protein kinase B (PKB), is a serine/threonine kinase downstream target of PI3K. Recent studies in the fructose-fed hamster model of insulin resistance have shown that hepatic very-low-density lipoprotein (VLDL) secretion is associated with reduced phosphorylation of Akt, suggesting a potential link between Akt expression and/or activity and apoB production in hepatocytes.