| First Author | Kim SW | Year | 2003 |
| Journal | Mol Cell Biol | Volume | 23 |
| Issue | 10 | Pages | 3583-92 |
| PubMed ID | 12724417 | Mgi Jnum | J:83272 |
| Mgi Id | MGI:2660917 | Doi | 10.1128/MCB.23.10.3583-3592.2003 |
| Citation | Kim SW, et al. (2003) Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice. Mol Cell Biol 23(10):3583-92 |
| abstractText | Activating signal cointegrator 2 (ASC-2), a cancer-amplified transcriptional coactivator of nuclear receptors and many other transcription factors, contains two LXXLL-type nuclear receptor interaction domains. Interestingly, the second LXXLL motif is highly specific to the liver X receptors (LXRs). In cotransfection, DN2, an ASC-2 fragment encompassing this motif, exerts a potent dominant-negative effect on transactivation by LXRs, which is rescued by ectopic coexpression of the full-length ASC-2 but not by other LXXLL-type coactivators, such as SRC-1 and TRAP220. In contrast, DN2/m, in which the LXXLL motif is mutated to LXXAA to abolish the interactions with LXRs, is without any effect. Accordingly, expression of DN2, but not DN2/m, in transgenic mice results in phenotypes that are highly homologous to those previously observed with LXRalpha(-/-) mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRalpha in the liver upon being fed a high-cholesterol diet. These results identify ASC-2 as a physiologically important transcriptional coactivator of LXRs and demonstrate its pivotal role in the liver lipid metabolism. |
