Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

Molecular cell | Apr 6, 2017

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

Pubmed ID: 28388439 RIS Download

Mesh terms: Active Transport, Cell Nucleus | Animals | Anti-Inflammatory Agents | Autophagy | Chemical and Drug Induced Liver Injury | Disease Models, Animal | Female | Genotype | HEK293 Cells | HeLa Cells | Hep G2 Cells | Humans | Ligands | Male | Mice, Inbred C57BL | Mice, Knockout | Mitochondria, Liver | Mitochondrial Degradation | Nuclear Receptor Subfamily 4, Group A, Member 1 | Phenotype | Protein Binding | Protein Interaction Domains and Motifs | RNA Interference | Sequestosome-1 Protein | Signal Transduction | TNF Receptor-Associated Factor 2 | Transfection | Triterpenes | Ubiquitination

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

ZEN Digital Imaging for Light Microscopy

User interface software for Carl Zeiss light microscopy imaging systems. After selecting a fluorophore, ZEN applies the necessary settings to collect and organize data.


View all literature mentions

Graphpad Prism

Statistical software package for data analysis, hypothesis testing, and modeling. The software can capable perform mathematical calculations (including biostatistics) and graphical plotting such as curve fitting (nonlinear regression) and scientific graphing.


View all literature mentions

Olympus Fluoview FV10-ASW

Image processing software used to modify and clarify sample images for FluoView FV1000 range of confocal laser scanning microscopes and Fluoview FV1000MPE multiphoton excitation systems. The software incorporates high-dynamic-range imaging, minimized signal-to-noise ratios, partial stitching with multiarea time-lapse imaging, and channel unmixing. The software also allows users to select specific areas of the whole sample, which can stitched together.


View all literature mentions