The Tnfaip8-PE complex is a novel upstream effector in theantiautophagic action of insulin

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486149.do
DOI
10.1038/s41598-017-06576-3
Title
The Tnfaip8-PE complex is a novel upstream effector in theantiautophagic action of insulin
Description
This work was supported by the grants (2015R1D1A1A01058942 to DHS and2016R1D1A1A09918309 and 2015M3C7A1028373 to JHS) from the NationalResearch Foundation of Korea (NRF) funded by the Ministry of Education.
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 G alpha i3 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 Gai3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 (A) over circle together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with G alpha i3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with G alpha i3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active G alpha i3 during insulin-induced anti-autophagy.
provenance
Made available in Cube on 2018-09-28T15:59:49Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Ji-Soo
Park, Jimin
Kim, Mi-Sun
Ha, Ji-Young
Jang, Ye-Won
Shin, Dong Hae
Son, Jin H.
accessioned
2018-09-28T15:59:49Z
available
2018-09-28T15:59:49Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486149.do
Funder
과학기술정보통신부
Funding Program
뇌과학원천기술개발
Project ID
1711056281
Jurisdiction
Rep.of Korea
Project Name
Technology Development for Early Detection of Posttraumatic Syndrome
rights
openAccess
type
article


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