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.
Averous
Julien
J
Unité de Nutrition et Métabolisme Protéique, INRA de Theix, Saint Genès Champanelle, France.
Maurin
Anne-Catherine
AC
Bruhat
Alain
A
Jousse
Céline
C
Arliguie
Céline
C
Fafournoux
Pierre
P
D020413:3' Untranslated Regions; D000596:Amino Acids / Q000172:deficiency / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000172:deficiency; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D020413:3' Untranslated Regions; D000596:Amino Acids; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D010761:Phosphorus Radioisotopes; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007930:Leucine