PMID- 28740220
OWN - NLM
STAT- MEDLINE
DCOM- 20190306
LR  - 20190306
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 24
TI  - The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action 
      of insulin.
PG  - 6248
LID - 10.1038/s41598-017-06576-3 [doi]
LID - 6248
AB  - 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.
FAU - Kim, Ji-Soo
AU  - Kim JS
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea.
FAU - Park, Jimin
AU  - Park J
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea.
FAU - Kim, Mi-Sun
AU  - Kim MS
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea.
FAU - Ha, Ji-Young
AU  - Ha JY
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea.
FAU - Jang, Ye-Won
AU  - Jang YW
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea.
FAU - Shin, Dong Hae
AU  - Shin DH
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea. 
      dhshin55@ewha.ac.kr.
FAU - Son, Jin H
AU  - Son JH
AD  - College of Pharmacy and Graduate School of Pharmaceutical Sciences, Global Top5 
      Research Program, Ewha W. University, Seoul, 03760, Republic of Korea. 
      hjson@ewha.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170724
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Insulin)
RN  - 0 (Phosphatidylethanolamines)
RN  - 0 (TNFAIP8 protein, mouse)
RN  - 39382-08-6 (phosphatidylethanolamine)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis Regulatory Proteins/*chemistry/*metabolism
MH  - *Autophagy
MH  - Crystallography, X-Ray
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/chemistry/*metabolism
MH  - Insulin/*metabolism
MH  - Mice
MH  - Phosphatidylethanolamines/chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Sequence Homology
PMC - PMC5524748
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/26 06:00
MHDA- 2019/03/07 06:00
PMCR- 2017/07/24
CRDT- 2017/07/26 06:00
PHST- 2016/11/23 00:00 [received]
PHST- 2017/06/15 00:00 [accepted]
PHST- 2017/07/26 06:00 [entrez]
PHST- 2017/07/26 06:00 [pubmed]
PHST- 2019/03/07 06:00 [medline]
PHST- 2017/07/24 00:00 [pmc-release]
AID - 10.1038/s41598-017-06576-3 [pii]
AID - 6576 [pii]
AID - 10.1038/s41598-017-06576-3 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 24;7(1):6248. doi: 10.1038/s41598-017-06576-3.