期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1821, 期 11, 页码 1443-1452出版社
ELSEVIER
DOI: 10.1016/j.bbalip.2012.07.004
关键词
FXR; Post-translational modification; Transactivation; Transrepression; Selective ligand; Nuclear receptor
资金
- Netherlands Organization for Scientific Research (NWO) Project VIDI [917.11.365]
- Utrecht University Support Grant
- Wilhelmina Children's Hospital Research Fund
- FP7-PEOPLE IEF [302867]
The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor (NR) superfamily. FXR plays an important role in positively regulating genes (transactivation) involved in bile acid homeostasis, fat and glucose metabolism. Recently, it has become clear that an additional important role for FXR consists of downregulating genes involved in inflammation. Because of this broad spectrum of regulated genes, therapeutically targeting FXR with full agonists will likely result in adverse side effects, in line with what is described for other NRs. It may therefore be necessary to develop selective FXR modulators. However, the molecular mechanisms that distinguish between FXR-mediated transactivation and transrepression are currently unknown. For other NRs, post-translational modifications such as SUMOylation and phosphorylation have been reported to be unique to either transactivation or transrepression. Here, we review current knowledge on post-translational regulation of FXR with respect to transac-tivation and transrepression. Ultimately, increased understanding of the different mechanisms of transactivation and transrepression of nuclear receptors will aid in the development of NR drugs with fewer side effects. (c) 2012 Elsevier B.V. All rights reserved.
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