Abstract
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.
MeSH terms
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3' Untranslated Regions*
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Amino Acids / deficiency
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Amino Acids / physiology*
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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Humans
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Insulin-Like Growth Factor Binding Protein 1
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Insulin-Like Growth Factor Binding Proteins / genetics
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Insulin-Like Growth Factor Binding Proteins / metabolism*
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Leucine / deficiency
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Phosphorus Radioisotopes / metabolism
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Pregnancy Proteins / genetics
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Pregnancy Proteins / metabolism*
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RNA, Messenger / metabolism*
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RNA, Small Interfering / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription, Genetic
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Transcriptional Activation*
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Transfection
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Up-Regulation
Substances
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3' Untranslated Regions
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Amino Acids
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IGFBP1 protein, human
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Insulin-Like Growth Factor Binding Protein 1
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Insulin-Like Growth Factor Binding Proteins
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Phosphorus Radioisotopes
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Pregnancy Proteins
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RNA, Messenger
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RNA, Small Interfering
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Leucine