| First Author | Odisho T | Year | 2015 |
| Journal | Exp Cell Res | Volume | 330 |
| Issue | 1 | Pages | 111-22 |
| PubMed ID | 25447309 | Mgi Jnum | J:218780 |
| Mgi Id | MGI:5618379 | Doi | 10.1016/j.yexcr.2014.10.007 |
| Citation | Odisho T, et al. (2015) ATF6beta regulates the Wfs1 gene and has a cell survival role in the ER stress response in pancreatic beta-cells. Exp Cell Res 330(1):111-22 |
| abstractText | Endoplasmic reticulum (ER) stress is implicated in pancreatic beta-cell dysfunction and death resulting in type 2 diabetes. Activating transcription factor 6 (ATF6) is an essential component of the Unfolded Protein Response (UPR) and consists of two isoforms, ATF6alpha and ATF6beta. Here we investigated the role of ATF6beta. ATF6beta mRNA was detected in pancreatic beta-cell lines and rodent and human islets. We also detected ATF6beta protein and production of the active form (ATF6betap60) in response to ER stress. Knock-down of ATF6beta in INS-1 832/13 insulinoma cells did not affect mRNA induction of several major UPR genes in response to ER stress, suggesting ATF6beta is not essential for the basic UPR. Expressing active ATF6betap60 or ATF6alphap50 followed by microarray analysis showed that they regulate similar UPR genes, although some genes such as Wfs1 are ATF6beta-specific. ATF6beta, but not ATF6alpha, is able to bind the Wfs1 promoter and induce Wfs1 gene and protein expression. Knock-down of ATF6beta increased the susceptibility of beta-cells to ER stress-induced apoptosis, while overexpression of active ATF6betap60 reduced apoptosis. Thus, ATF6beta is not essential for induction of most UPR genes, but is required to maintain cell survival in beta-cells undergoing chronic ER stress, which in part relates to its ability to induce Wfs1, a pro-survival gene. |
