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.