Pancreatic duodenal homeobox factor-1 and diabetes mellitus type 2 (review).

Abstract

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.

• Authors: Faizeh Al-Quobaili, Mathias Montenarh
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 21 Issue 4 Pg. 399-404 (Apr 2008) ISSN: 1107-3756 [Print] Greece
• PMID: 18360684 (Publication Type: Journal Article, Review)

Chemical References

• Homeodomain Proteins
• Trans-Activators
• pancreatic and duodenal homeobox 1 protein

Topics

• Binding Sites
• Diabetes Mellitus, Type 2 (etiology, genetics, metabolism)
• Homeodomain Proteins (chemistry, genetics, metabolism)
• Humans
• Pancreas (metabolism)
• Protein Processing, Post-Translational
• Protein Structure, Tertiary
• Trans-Activators (chemistry, genetics, metabolism)
• Transcription, Genetic