PMID- 19726677
OWN - NLM
STAT- MEDLINE
DCOM- 20091214
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 44
DP  - 2009 Oct 30
TI  - Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages 
      by suppressing the activity of factor inhibiting HIF-1.
PG  - 30350-9
LID - 10.1074/jbc.M109.019216 [doi]
AB  - Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor regulating 
      cellular responses to hypoxia and is composed of alpha and beta subunits. During 
      normoxia, factor inhibiting HIF-1 (FIH-1) inhibits the activity of HIF-1 by 
      preventing HIF-1alpha binding to p300/CBP via modification of the Asn(803) 
      residue. However, it is not known whether FIH-1 activity can be regulated in an 
      oxygen-independent manner. In this study, we survey possible binding proteins to 
      FIH-1 and identify Mint3/APBA3, which has been reported to bind Alzheimer 
      beta-amyloid precursor protein. Purified Mint3 binds FIH-1 and inhibits the 
      ability of FIH-1 to modify HIF-1alpha in vitro. In a reporter assay, the activity 
      of HIF-1alpha is suppressed because of endogenous FIH-1 in HEK293 cells, and 
      expression of Mint3 antagonizes this suppression. Macrophages are known to depend 
      on glycolysis for ATP production because of elevated HIF-1 activity. FIH-1 
      activity is suppressed in macrophages by Mint3 so as to maintain HIF-1 activity. 
      FIH-1 forms a complex with Mint3, and these two factors co-localize within the 
      perinuclear region. Knockdown of Mint3 expression in macrophages leads to 
      redistribution of FIH-1 to the cytoplasm and decreases glycolysis and ATP 
      production. Thus, Mint3 regulates the FIH-1-HIF-1 pathway, which controls ATP 
      production in macrophages and therefore represents a potential new therapeutic 
      target to regulate macrophage-mediated inflammation.
FAU - Sakamoto, Takeharu
AU  - Sakamoto T
AD  - Division of Cancer Cell Research, Institute of Medical Science, The University of 
      Tokyo, Shirokanedai, Tokyo 108-8639, Japan.
FAU - Seiki, Motoharu
AU  - Seiki M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090902
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (APBA3 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Repressor Proteins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.11.- (HIF1AN protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adenosine Triphosphate/biosynthesis
MH  - Carrier Proteins/*physiology
MH  - Glycolysis
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/agonists/metabolism
MH  - Macrophages/*metabolism
MH  - Mixed Function Oxygenases
MH  - Protein Binding
MH  - Protein Transport
MH  - Repressor Proteins/antagonists & inhibitors/*metabolism
PMC - PMC2781590
EDAT- 2009/09/04 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/30
CRDT- 2009/09/04 06:00
PHST- 2009/09/04 06:00 [entrez]
PHST- 2009/09/04 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/30 00:00 [pmc-release]
AID - S0021-9258(20)38090-X [pii]
AID - M109.019216 [pii]
AID - 10.1074/jbc.M109.019216 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Oct 30;284(44):30350-9. doi: 10.1074/jbc.M109.019216. Epub 2009 
      Sep 2.