Insulin-response Element-binding Protein 1

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.