Role of MafA in pancreatic beta-cells.
Pancreatic beta-cell-specific insulin gene expression is regulated by a variety of pancreatic transcription factors and the conserved A3, C1 and E1 elements in the insulin gene enhancer region are very important for activation of insulin gene. Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. These results suggest that MafA plays a crucial role in pancreatic beta-cells and could be a novel therapeutic target for diabetes.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med.osaka-u.ac.jp
Matsuoka
Taka-Aki
TA
Kawashima
Satoshi
S
Yamamoto
Kaoru
K
Kato
Ken
K
Miyatsuka
Takeshi
T
Katakami
Naoto
N
Matsuhisa
Munehide
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051473:Maf Transcription Factors, Large / Q000235:genetics* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C485159:MAFA protein, human; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1