PMID- 35609419
OWN - NLM
STAT- MEDLINE
DCOM- 20220620
LR  - 20220711
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 615
DP  - 2022 Jul 30
TI  - IRF2BP2 is a novel HNF4alpha co-repressor: Its role in gluconeogenic gene regulation 
      via biochemically labile interaction.
PG  - 81-87
LID - S0006-291X(22)00675-1 [pii]
LID - 10.1016/j.bbrc.2022.04.133 [doi]
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) has essential roles in controlling the 
      expression of a variety of genes involved in key metabolic pathways, including 
      gluconeogenesis in the liver. The mechanistic and physiological significance of 
      peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) for 
      HNF4alpha-mediated transcriptional activation models for gluconeogenic genes is well 
      characterized. However, the transcriptional repression of HNF4alpha for those genes 
      remains to be examined. In this study, we applied novel proteomic techniques to 
      evaluate the interactions of HNF4alpha, including those with biochemically labile 
      binding proteins. Based upon our experiments, we identified interferon regulatory 
      factor 2 binding protein 2 (IRF2BP2) as a novel HNF4alpha co-repressor. This 
      interaction could not be detected by conventional immunoprecipitation. IRF2BP2 
      repressed the transcriptional activity of HNF4alpha dependent on its E3 ubiquitin 
      ligase activity. Deficiency of the IRF2BP2 gene in HepG2 cells induced 
      gluconeogenic genes comparable to that of forskolin-treated wild-type HepG2 
      cells. Together, these results suggest that IRF2BP2 represents a novel class of 
      nuclear receptor co-regulator.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Kouketsu, Takumi
AU  - Kouketsu T
AD  - Department of Molecular Endocrinology, Tohoku University Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Monma, Rina
AU  - Monma R
AD  - Department of Molecular Endocrinology, Tohoku University Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Miyairi, Yuri
AU  - Miyairi Y
AD  - Department of Molecular Endocrinology, Tohoku University Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Sawatsubashi, Shun
AU  - Sawatsubashi S
AD  - Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical 
      Sciences, Tokushima University, Tokushima, 7708503, Tokushima, Japan.
FAU - Shima, Hiroki
AU  - Shima H
AD  - Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 
      Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Igarashi, Kazuhiko
AU  - Igarashi K
AD  - Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 
      Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Sugawara, Akira
AU  - Sugawara A
AD  - Department of Molecular Endocrinology, Tohoku University Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
FAU - Yokoyama, Atsushi
AU  - Yokoyama A
AD  - Department of Molecular Endocrinology, Tohoku University Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan. Electronic 
      address: ayokoyama@med.tohoku.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220518
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Hepatocyte Nuclear Factor 4)
SB  - IM
MH  - Co-Repressor Proteins/metabolism
MH  - Gene Expression Regulation
MH  - *Gluconeogenesis/genetics
MH  - *Hepatocyte Nuclear Factor 4/genetics/metabolism
MH  - Liver/metabolism
MH  - Proteomics
OTO - NOTNLM
OT  - Gluconeogenesis
OT  - HNF4alpha
OT  - IRF2BP2
OT  - Liver
OT  - Nuclear receptor
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/05/25 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/05/24 18:20
PHST- 2022/04/22 00:00 [received]
PHST- 2022/04/27 00:00 [accepted]
PHST- 2022/05/25 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/05/24 18:20 [entrez]
AID - S0006-291X(22)00675-1 [pii]
AID - 10.1016/j.bbrc.2022.04.133 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2022 Jul 30;615:81-87. doi: 
      10.1016/j.bbrc.2022.04.133. Epub 2022 May 18.