Abstract
HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 14-20 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 468 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Dec 4 2015 |
Bibliographical note
Funding Information:We wish to thank Dr. Sabire Őzcan at the University of Kentucky for a kind gift of MIN6 cell cDNA library for yeast two-hybrid screenings and MIN6 cells for functional studies. This work was funded by the American Diabetes Association ( 7-08-CD-03 ) and the NIH Grant P20RR20171 from the COBRE program of the National Center for Research Resources .
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
Keywords
- AES
- Diabetes
- Gene regulation
- HNF1α
- Homeodomain
- Insulin secretion
- POU transcription factor
- Protein-protein interaction
