| First Author | Yeom SY | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 12 | Pages | 4553-63 |
| PubMed ID | 16738321 | Mgi Jnum | J:109607 |
| Mgi Id | MGI:3629357 | Doi | 10.1128/MCB.01412-05 |
| Citation | Yeom SY, et al. (2006) Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2. Mol Cell Biol 26(12):4553-63 |
| abstractText | Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic beta-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/- mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/- mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/- islets. These results suggest that ASC-2 regulates insulin secretion and beta-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes. |
