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The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin
- Title
- The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin
- Authors
- Kim J.-S.; Park J.; Kim M.-S.; Ha J.-Y.; Jang Y.-W.; Shin D.H.; Son J.H.
- Ewha Authors
- 손형진; 신동해
- SCOPUS Author ID
- 손형진; 신동해
- Issue Date
- 2017
- Journal Title
- Scientific Reports
- ISSN
- 2045-2322
- Citation
- Scientific Reports vol. 7, no. 1
- Publisher
- Nature Publishing Group
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Defective hepatic autophagy is observed in obesity and diabetes, whereas autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy is mediated by non-canonical Gαi3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 via activation of mammalian target of rapamycin (mTOR) in the nervous system. Here, we demonstrate that insulin temporally induces Tnfaip8, which mediates the anti-autophagic action of insulin through formation of a novel ternary complex including Tnfaip8, phosphatidylethanolamine (PE) and Gαi3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 Å together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Gαi3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Gαi3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Gαi3 during insulin-induced anti-autophagy. © 2017 The Author(s).
- DOI
- 10.1038/s41598-017-06576-3
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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