PMID- 27810898
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20231213
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 52
DP  - 2016 Dec 23
TI  - MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) Interaction Disruptor 
      Sensitizes Insulin Signaling in Skeletal Muscle.
PG  - 26627-26635
LID - 10.1074/jbc.M116.754424 [doi]
AB  - Mitsugumin 53 (MG53) is an E3 ligase that interacts with and ubiquitinates 
      insulin receptor substrate-1 (IRS-1) in skeletal muscle; thus, an MG53-IRS-1 
      interaction disruptor (MID), which potentially sensitizes insulin signaling with 
      an elevated level of IRS-1 in skeletal muscle, is an excellent candidate for 
      treating insulin resistance. To screen for an MID, we developed a bimolecular 
      luminescence complementation system using an N-terminal luciferase fragment fused 
      with IRS-1 and a C-terminal luciferase fragment fused with an MG53 C14A mutant 
      that binds to IRS-1 but does not have E3 ligase activity. An MID, which was 
      discovered using the bimolecular luminescence complementation system, disrupted 
      the molecular association of MG53 with IRS-1, thus abolishing MG53-mediated IRS-1 
      ubiquitination and degradation. Thus, the MID sensitized insulin signaling and 
      increased insulin-elicited glucose uptake with an elevated level of IRS-1 in 
      C2C12 myotubes. These data indicate that this MID holds promise as a drug 
      candidate for treating insulin resistance.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Lee, Hyun
AU  - Lee H
AD  - From the Division of Life Sciences and.
FAU - Park, Jung-Jin
AU  - Park JJ
AD  - From the Division of Life Sciences and.
FAU - Nguyen, Nga
AU  - Nguyen N
AD  - From the Division of Life Sciences and.
FAU - Park, Jun Sub
AU  - Park JS
AD  - From the Division of Life Sciences and.
FAU - Hong, Jin
AU  - Hong J
AD  - From the Division of Life Sciences and.
FAU - Kim, Seung-Hyeob
AU  - Kim SH
AD  - From the Division of Life Sciences and.
FAU - Song, Woon Young
AU  - Song WY
AD  - the Department of Chemistry, Korea University, Seoul, 02841, Korea.
FAU - Kim, Hak Joong
AU  - Kim HJ
AD  - the Department of Chemistry, Korea University, Seoul, 02841, Korea.
FAU - Choi, Kwangman
AU  - Choi K
AD  - the Targeted Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, 34141, Korea, and.
FAU - Cho, Sungchan
AU  - Cho S
AD  - the Targeted Medicine Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, 34141, Korea, and.
FAU - Lee, Jae-Seon
AU  - Lee JS
AD  - the Department of Biomedical Sciences, College of Medicine, Inha University, 
      Incheon, 22212, Korea.
FAU - Kim, Bong-Woo
AU  - Kim BW
AUID- ORCID: 0000-0001-8767-9519
AD  - From the Division of Life Sciences and kbw96@korea.ac.kr.
FAU - Ko, Young-Gyu
AU  - Ko YG
AD  - From the Division of Life Sciences and ygko@korea.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20161103
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Microtubule Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Small Molecule Libraries)
RN  - 0 (TRIM72 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (MID1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - Insulin Resistance
MH  - Microtubule Proteins/*metabolism
MH  - Muscle Fibers, Skeletal/cytology/drug effects/metabolism
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Interaction Maps/*drug effects
MH  - Proteolysis
MH  - Signal Transduction/drug effects
MH  - Small Molecule Libraries/*pharmacology
MH  - Transcription Factors/*metabolism
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Ubiquitination
PMC - PMC5207173
OTO - NOTNLM
OT  - diabetes
OT  - drug discovery
OT  - insulin receptor substrate 1 (IRS-1)
OT  - insulin resistance
OT  - skeletal muscle
EDAT- 2016/11/05 06:00
MHDA- 2017/06/02 06:00
PMCR- 2017/12/23
CRDT- 2016/11/05 06:00
PHST- 2016/08/18 00:00 [received]
PHST- 2016/11/01 00:00 [revised]
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
PHST- 2016/11/05 06:00 [entrez]
PHST- 2017/12/23 00:00 [pmc-release]
AID - S0021-9258(20)34417-3 [pii]
AID - M116.754424 [pii]
AID - 10.1074/jbc.M116.754424 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Dec 23;291(52):26627-26635. doi: 10.1074/jbc.M116.754424. Epub 
      2016 Nov 3.