Pancreatic duodenal homeobox factor-1 and diabetes mellitus type 2 (review).
The homeobox domain transcription factor PDX-1 is essential for pancreatic development and for the maintenance of beta-cell function. The participation of pancreatic duodenal homeobox factor-1 (PDX-1) in the transcription of several genes which are essential for glucose sensing and insulin synthesis underlines its key role in beta-cells of the pancreas. PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression. By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter. Ectopic expression of PDX-1 together with other cofactors can re-program cells to behave like beta-cells and produce insulin. This property of PDX-1 opens new strategies for the treatment of diabetes. Little is known about its regulation at the posttranslational level. Here, we report on its DNA-binding activity, the nuclear import and on post-translational modifications such as phosphorylation, glycosylation and sumoylation. Modulation of these post-translational modifications may be an alternate strategy for treating diabetes.
Al-Quobaili
Faizeh
F
Medical Biochemistry and Molecular Biology, University of the Saarland, D-66424 Homburg, Germany.
Montenarh
Mathias
M
D001665:Binding Sites; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein