How triciribine works on Akt/PKB signaling?
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Triciribine, a highly selective AKT inhibitor, works on Akt/PKB signaling by increasing the stability of low-density lipoprotein receptor (LDLR) mRNA and upregulating LDLR expression . Triciribine activates extracellular signal-regulated kinase (ERK) signaling, which leads to the translocation of Hu antigen R (HuR) from the nucleus to the cytoplasm, thereby increasing the activity of HuR and stabilizing LDLR mRNA . Triciribine also inhibits the RNA-binding protein ZFP36 ring finger protein like 1 (ZFP36L1), which destabilizes LDLR mRNA . Additionally, triciribine downregulates the expression of PCSK9 mRNA and blunts the secretion of its protein, further enhancing LDLR levels and activity . Triciribine's effect on LDLR expression is partially dependent on the intervening sequence in LDLR 3′UTR . Triciribine has also been shown to synergistically enhance the cytotoxic activity of gemcitabine in pancreatic cancer cells by inhibiting Akt/PKB signaling .
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