Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice
- Title
- Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice
- Author
- 황승용
- Issue Date
- 2003-07
- Publisher
- AMER SOC MICROBIOLOGY
- Citation
- Molecular and cellular biology v. 23, no. 10, page. 3583-3592
- 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 LXRα−/− mice, including a rapid accumulation of large amounts of cholesterol and down-regulation of the known lipid-metabolizing target genes of LXRα 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC164762/?tool=pubmedhttps://repository.hanyang.ac.kr/handle/20.500.11754/156101
- ISSN
- 3583–3592
- DOI
- 10.1128/MCB.23.10.3583-3592.2003
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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