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Publication Abstract from PubMed

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 Galphai3 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 Galphai3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 A together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Galphai3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Galphai3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Galphai3 during insulin-induced anti-autophagy.

The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin.,Kim JS, Park J, Kim MS, Ha JY, Jang YW, Shin DH, Son JH Sci Rep. 2017 Jul 24;7(1):6248. doi: 10.1038/s41598-017-06576-3. PMID:28740220^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.