PMID- 22634009
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 423
IP  - 1
DP  - 2012 Jun 22
TI  - Insulin/insulin-like growth factor (IGF) stimulation abrogates an association 
      between a deubiquitinating enzyme USP7 and insulin receptor substrates (IRSs) 
      followed by proteasomal degradation of IRSs.
PG  - 122-7
LID - 10.1016/j.bbrc.2012.05.093 [doi]
AB  - Insulin receptor substrates (IRSs) play central roles in insulin/insulin-like 
      growth factor (IGF) signaling and mediate a variety of their bioactivities. IRSs 
      are tyrosine-phosphorylated by activated insulin receptor/IGF-I receptor tyrosine 
      kinase in response to insulin/IGF, and are recognized by signaling molecules 
      possessing the SH2 domain such as phosphatidylinositol 3-kinase (PI3K), leading 
      to the activation of downstream pathways. Recent studies have suggested that 
      degradation of IRSs by the ubiquitin-proteasome pathway leads to impaired 
      insulin/IGF signaling, but the precise mechanism underlying the process is still 
      unclear. In this study, we identified deubiquitinating enzyme ubiquitin specific 
      protease 7 (USP7) as an IRS-2-interacting protein and demonstrated that 
      deubiquitinase activity of USP7 plays important roles in IRS-2 stabilization 
      through the ubiquitin-proteasome pathway. In addition, insulin treatment 
      dissociated USP7 from IRS-2, leading to degradation of IRS-2. This dissociation 
      was prevented by treatment with LY294002, a PI3K inhibitor, indicating that 
      insulin activation of the PI3K pathway leads to dissociation of IRS-2 from USP7 
      and IRS-2 degradation. We obtained similar results for IRS-1 in cells treated 
      with insulin and for IRS-2 in cells treated with IGF-I. Taken together, this is 
      the first report demonstrating that USP7 is an IRS-1/2 deubiquitinating enzyme 
      forming a negative feedback loop in insulin/IGF signaling.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Yoshihara, Hidehito
AU  - Yoshihara H
AD  - Department of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Fukushima, Toshiaki
AU  - Fukushima T
FAU - Hakuno, Fumihiko
AU  - Hakuno F
FAU - Saeki, Yasushi
AU  - Saeki Y
FAU - Tanaka, Keiji
AU  - Tanaka K
FAU - Ito, Akihiro
AU  - Ito A
FAU - Yoshida, Minoru
AU  - Yoshida M
FAU - Iemura, Shun-ichiro
AU  - Iemura S
FAU - Natsume, Tohru
AU  - Natsume T
FAU - Asano, Tomoichiro
AU  - Asano T
FAU - Chida, Kazuhiro
AU  - Chida K
FAU - Girnita, Leonard
AU  - Girnita L
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120523
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (IRS1 protein, human)
RN  - 0 (IRS2 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.19.12 (USP7 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Peptidase 7)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - HEK293 Cells
MH  - Humans
MH  - Insulin/*metabolism/pharmacology
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - Insulin-Like Growth Factor I/*metabolism/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Stability
MH  - Proteolysis
MH  - RNA, Small Interfering/genetics
MH  - Ubiquitin Thiolesterase/genetics/*metabolism
MH  - Ubiquitin-Specific Peptidase 7
EDAT- 2012/05/29 06:00
MHDA- 2012/09/14 06:00
CRDT- 2012/05/29 06:00
PHST- 2012/05/14 00:00 [received]
PHST- 2012/05/16 00:00 [accepted]
PHST- 2012/05/29 06:00 [entrez]
PHST- 2012/05/29 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
AID - S0006-291X(12)00983-7 [pii]
AID - 10.1016/j.bbrc.2012.05.093 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Jun 22;423(1):122-7. doi: 
      10.1016/j.bbrc.2012.05.093. Epub 2012 May 23.