0 77

Cited 0 times in

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

Authors
 Young Suk Jo  ;  Dongryeol Ryu  ;  Adriano Maida  ;  Xu Wang  ;  Ronald M. Evans  ;  Kristina Schoonjans  ;  Johan Auwerx 
Citation
 Hepatology, Vol.62(5) : 1606-1618, 2015 
Journal Title
 Hepatology 
ISSN
 0270-9139 
Issue Date
2015
Abstract
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 (PPARα) 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 PPARα and estrogen-related receptor alpha (ERRα) over liver X receptor alpha (LXRα). Phosphorylation of NCoR1 on S1460 selectively derepresses LXRα target genes, resulting in increased lipogenesis, whereas, at the same time, it inhibits PPARα and ERRα 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 LXRα, PPARα, and ERRα 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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140796
DOI
10.1002/hep.27907
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
조영석(Jo, Young Suk)
사서에게 알리기
  feedback
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/hep.27907/abstract
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse