An insulin-inducible transcription factor, SHARP-1, represses transcription of the longevity gene.

The rat genes encode insulin-inducible transcriptional repressors. A longevity gene, encodes protein deacetylase. These play an important role in regulating hepatic glucose metabolism. In this study, to evaluate a correlation with these gene expressions, we examined whether SIRT1 effects on expression of the -1 gene by a treatment with a SIRT1 inhibitor or activator in rat H4IIE hepatoma cells. Whereas the SIRT1 inhibitor increased the level of SHARP-1 mRNA, the SIRT1 activator decreased it. Next, whether SHARP-1 effect on the transcriptional activity of the human gene using luciferase reporter assays was determined. Promoter activity of the gene was specifically repressed by SHARP-1. Further reporter analysis using 5'- deleted or mutated constructs revealed that an E box sequence (5'-CACGTG-3') of the gene promoter was required for the inhibitory effect of SHARP-1. Thus, we conclude that expressions between the and the genes show a negative correlation and that SHARP-1 represses transcription of the gene.