4.8 Article

Phosphorylation of the nuclear receptor corepressor 1 by protein kinase B switches its corepressor targets in the liver in mice

期刊

HEPATOLOGY
卷 62, 期 5, 页码 1606-1618

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1002/hep.27907

关键词

-

资金

  1. EPFL
  2. National Institutes of Health [R01-AG043930]
  3. SNSF [31003A-140780, 310030-143748]
  4. National Research Foundation of Korea (NRF) - Korea government (MEST) [2012R1A2A2A01014672]
  5. Canadian Institutes of Health Research
  6. National Research Foundation of Korea [2012R1A2A2A01014672] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
  7. Swiss National Science Foundation (SNF) [310030_143748] Funding Source: Swiss National Science Foundation (SNF)

向作者/读者索取更多资源

Nuclear receptor corepressor 1 (NCoR1) is a transcriptional coregulator that has wide-ranging effects on gene expression patterns. In the liver, NCoR1 represses lipid synthesis in the fasting state, whereas it inhibits activation of peroxisome proliferator-activated receptor alpha (PPAR) upon feeding, thereby blunting ketogenesis. Here, we show that insulin by activation of protein kinase B induces phosphorylation of NCoR1 on serine 1460, which selectively favors its interaction with PPAR and estrogen-related receptor alpha (ERR) over liver X receptor alpha (LXR). Phosphorylation of NCoR1 on S1460 selectively derepresses LXR target genes, resulting in increased lipogenesis, whereas, at the same time, it inhibits PPAR and ERR targets, thereby attenuating oxidative metabolism in the liver. Phosphorylation-gated differential recruitment of NCoR1 to different nuclear receptors explains the apparent paradox that liver-specific deletion of NCoR1 concurrently induces both lipogenesis and oxidative metabolism owing to a global derepression of LXR, PPAR, and ERR activity. Conclusion: Phosphorylation-mediated recruitment switch of NCoR1 between nuclear receptor subsets provides a mechanism by which corepressors can selectively modulate liver energy metabolism during the fasting-feeding transition. (Hepatology 2015;62:1606-1618)

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据