Induction of IGFBP-1 expression by amino acid deprivation of HepG2 human hepatoma cells involves both a transcriptional activation and an mRNA stabilization due to its 3′UTR

A dramatic overexpression of IGFBP-1 is responsible for growth inhibition, in response to a low-protein diet feeding. It has been demonstrated that a fall in the amino acid concentration was directly responsible for IGFBP-1 induction. In this report, we sought to determine the mechanism by which amino acid limitation upregulates IGFBP-1 expression. Our results show that both transcriptional activation and mRNA stabilization are involved. We also demonstrate that (i) the mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3′UTR of IGFBP-1 mRNA is responsible for its destabilization and regulates its stability in response to amino acid starvation.