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RIP140, a Janus metabolic switch involved in defense functions

Cellular & Molecular Immunology volume 10, pages 7–9 (2013)Cite this article

Since its discovery almost 15 years ago, the receptor-interacting protein RIP140 has been determined to be a corepressor of various transcription factors and nuclear receptors. Mice lacking the RIP140 gene are lean, exhibit resistance to high-fat diet-induced obesity and have increased glucose tolerance and insulin sensitivity. In 2008, RIP140 was determined to be a coactivator of nuclear factor-κB, a master transcriptional regulator of inflammation in immune cells, including macrophages. This year, it was reported that RIP140 degradation is involved in the resolution of inflammation and in endotoxin tolerance. The general picture that had emerged indicates that RIP140 is a Janus metabolic switch that convergently regulates metabolic pathways involved in defense functions through its pleotropic interactions with transcription factors.

RIP140 was first identified by its ability to interact with estrogen receptors and has been shown to repress their transcriptional activity. Later studies revealed that RIP140 binds and represses a number of other nuclear receptors, including PPARs (PPARα, PPARβ, PPARγ), estrogen-related receptors (ERRα and ERRβ) and thyroid hormone receptors (TRα and TRβ). Researchers have demonstrated that the ability of RIP140 to regulate nuclear receptor function is determined by the relative level of RIP140 expression in comparison with other cofactors, by post-translational modifications, and by interactions with additional transcriptional factors. RIP140 post-translational modifications are chemically diverse. RIP140 primarily functions as a scaffold protein that links nuclear receptors to chromatin remodeling enzymes involved in chromatin condensation and transcriptional repression.3

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  1. School of Biological Sciences, University of Ulsan, Meta-Inflammation Basic Research Laboratory, Ulsan, Korea

    Hun Taeg Chung

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  1. Hun Taeg Chung
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Correspondence to Hun Taeg Chung.

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Chung, H. RIP140, a Janus metabolic switch involved in defense functions. Cell Mol Immunol 10, 7–9 (2013). https://doi.org/10.1038/cmi.2012.53

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