| First Author | Sato Y | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 27 | Pages | 23236-45 |
| PubMed ID | 22589549 | Mgi Jnum | J:188369 |
| Mgi Id | MGI:5440380 | Doi | 10.1074/jbc.M112.368779 |
| Citation | Sato Y, et al. (2012) Anks4b, a novel target of HNF4alpha protein, interacts with GRP78 protein and regulates endoplasmic reticulum stress-induced apoptosis in pancreatic beta-cells. J Biol Chem 287(27):23236-45 |
| abstractText | Mutations of the HNF4A gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of pancreatic beta-cell function. HNF4alpha is a transcription factor belonging to the nuclear receptor superfamily (NR2A1), but its target genes in pancreatic beta-cells are largely unknown. Here, we report that ankyrin repeat and sterile alpha motif domain containing 4b (Anks4b) is a target of HNF4alpha in pancreatic beta-cells. Expression of Anks4b was decreased in both betaHNF4alpha KO islets and HNF4alpha knockdown MIN6 beta-cells, and HNF4alpha activated Anks4b promoter activity. Anks4b bound to glucose-regulated protein 78 (GRP78), a major endoplasmic reticulum (ER) chaperone protein, and overexpression of Anks4b enhanced the ER stress response and ER stress-associated apoptosis of MIN6 cells. Conversely, suppression of Anks4b reduced beta-cell susceptibility to ER stress-induced apoptosis. These results indicate that Anks4b is a HNF4alpha target gene that regulates ER stress in beta-cells by interacting with GRP78, thus suggesting that HNF4alpha is involved in maintenance of the ER. |
