Insulin-response element-binding protein 1: a novel Akt substrate involved in transcriptional action of insulin.
Although the cis-acting elements that mediate the actions of insulin on gene transcription have been defined for a significant number of genes, the transcription factors responsible for the transactivation of these target sequences remain unknown. In this report, we identified a novel transcription factor that binds and transactivates the insulin-response elements of the insulin-like growth factor-binding protein-3 and other insulin responsive genes. This factor is a target of insulin signal transduction downstream of the phosphatidylinositol 3'-kinase/protein kinase B (Akt) pathway. Akt phosphorylates this factor in vivo and in vitro. Changes in expression level, phosphorylation, and nuclear translocation modulate the transactivation effects of the factor, and its expression is decreased in conditions of diabetes and insulin deficiency. Identification of a novel target of Akt that appears to mediate signals specific for insulin action should provide further insight into the mechanism of insulin action at the genomic level.
Villafuerte
Betty C
BC
Division of Endocrinology and Metabolism, Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Phillips
Lawrence S
LS
Rane
Madhavi J
MJ
Zhao
Weidong
W
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D015723:Gene Library; D017930:Genes, Reporter; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C484091:insulin response element binding protein, rat; C075372:insulin response element binding protein, human; D004247:DNA; D008156:Luciferases; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt