Thyroid hormone receptor interacting protein 3 (trip3) is a novel coactivator of hepatocyte nuclear factor-4alpha.
Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. HNF-4alpha, which is a transcription factor expressed in pancreatic beta-cells, plays an important role in regulating the ... expression of genes involved in glucose metabolism. Thus, cofactors that interact with HNF-4alpha and modify its transcriptional activity might also play an important role in regulating the metabolic pathways in pancreatic beta-cells, and the genes of such cofactors are plausible candidate genes for MODY. In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. Human Trip3 cDNA contained an open reading frame for a protein of 155 amino acids, and the gene was expressed in both pancreatic islets and MIN6 cells. Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. These results suggest that Trip3 is a coactivator of HNF-4alpha. Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha.
Mesh Terms:
Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, COS Cells, Cercopithecus aethiops, Cloning, Molecular, DNA Primers, DNA-Binding Proteins, Hepatocyte Nuclear Factor 4, Humans, Islets of Langerhans, Liver, Phosphoproteins, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transfection
Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, COS Cells, Cercopithecus aethiops, Cloning, Molecular, DNA Primers, DNA-Binding Proteins, Hepatocyte Nuclear Factor 4, Humans, Islets of Langerhans, Liver, Phosphoproteins, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transfection
Diabetes
Date: Apr. 01, 2002
PubMed ID: 11916906
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