1. Tetrapeptide KEDW Interacts with DNA and Regulates Gene Expression.
- Author
-
Khavinson, V. Kh., Tendler, S. M., Kasyanenko, N. A., Tarnovskaya, S. I., Linkova, N. S., Ashapkin, V. V., Yakutseni, P. P., and Vanyushin, B. F.
- Subjects
- *
PEPTIDES , *DIABETES , *PROTEIN synthesis - Abstract
Peptide KEDW (Lys-Glu-Asp-Trp-NH2) is known to reduce the blood glucose level in rats with streptozotocin- and alloxan-induced diabetes mellitus. Here, we examine the influence of KEDW peptide on cell differentiation and DNA structure. KEDW peptide increased the expression of PDX1, NGN3, PAX6, FOXA2, NKX2-2, NKX6.1, and PAX4 genes but decreased MNX1 and HOXA3 gene expression when added to pancreatic cell culture. Moreover, KEDW peptide caused an increase in expression of PDX1, NGN3, PAX6, FOXA2, NKX2-2, NKX6.1, and PAX4 proteins without affecting synthesis of MNX1 and HOXA3 when added to pancreatic cell culture. Results obtained through physical methods (UV-visible absorption, circular dichroism) and molecular modelling methods suggest that the peptide binds to DNA along the major groove. Experimental and theoretical data provided a 3D model of the stable DNA-peptide complex. We propose that regulation of differentiation factor expression in pancreatic (endocrine) cells by KEDW peptide occurs through specific binding of the peptide to regulatory elements of corresponding genes. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF