Roles and regulation of transcription factor MafA in islet beta-cells.
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.
Aramata
Shinsaku
S
Graduate School of Biological Science, Nara Institute of Science and Technology, Nara Japan.
Han
Song-Iee
SI
Kataoka
Kohsuke
K
D000818:Animals; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000502:physiology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009928:Organ Specificity; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology