Roles and regulation of transcription factor MafA in islet beta-cells

Abstract

Insulin is a critical hormone in the regulation of blood glucose levels. It is produced exclusively by pancreatic islet beta-cells. beta-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing beta-cell-specific insulin expression, and in the regulation of beta-cell differentiation. It was shown that MafA, a beta-cell-specific member of the Maf family of transcription factors, binds to the conserved C1/RIPE3b element of the insulin promoter. The Maf family proteins regulate tissue-specific gene expression and cell differentiation in a wide variety of tissues. MafA acts synergistically with Pdx1 and Beta2 to activate the insulin gene promoter, and mice with a targeted deletion of mafA develop age-dependent diabetes. MafA also regulates genes involved in beta-cell function such as Glucose transporter 2, Glucagons-like peptide 1 receptor, and Prohormone convertase 1/3. The abundance of MafA in beta-cells is regulated at both the transcriptional and post-translational levels by glucose and oxidative stress. This review summarizes recent progress in determining the functions and roles of MafA in the regulation of insulin gene transcription in beta-cells.