Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice
SCIE
SCOPUS
- Title
- Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice
- Authors
- Kim, SW; Park, K; Kwak, E; Choi, E; Lee, S; Ham, J; Kang, H; Kim, JM; Hwang, SY; Kong, YY; Lee, K; Lee, JW
- Date Issued
- 2003-05
- Publisher
- AMER SOC MICROBIOLOGY
- Abstract
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/11678
- DOI
- 10.1128/MCB.23.10.35
- ISSN
- 0270-7306
- Article Type
- Article
- Citation
- MOLECULAR AND CELLULAR BIOLOGY, vol. 23, no. 10, page. 3583 - 3592, 2003-05
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