Triciribine increases LDLR expression and LDL uptake through stabilization of LDLR mRNA.

ABSTRACT: Low-density lipoprotein receptor (LDLR) is a key regulator of the metabolism of plasma low-density lipoprotein cholesterol (LDL-C), the elevated levels of which are associated with an increased risk of cardiovascular disease. Therefore, enhancing LDLR expression represents a potent treatment strategy for hypercholesterolemia. Here, we report that in cultured human hepatoma cells, triciribine, a highly selective AKT inhibitor, increases the stability of LDLR mRNA, an event that translates into upregulation of cell-surface LDLR levels and induction of cellular LDL uptake. This effect of triciribine requires ERK activity and is partially dependent on the intervening sequence between the AU-rich elements ARE3 and ARE4 in LDLR 3'UTR. We also show that triciribine downregulates the expression of

SUBMITTER: Bjune K 

PROVIDER: S-EPMC6212527 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature