Reference - Detail
| RRC ID | 28624 |
|---|---|
| Author | Sakamoto T, Seiki M. |
| Title | Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1. |
| Journal | J Biol Chem |
| Abstract |
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. |
| Volume | 284(44) |
| Pages | 30350-9 |
| Published | 2009-10-30 |
| DOI | 10.1074/jbc.M109.019216 |
| PII | S0021-9258(20)38090-X |
| PMID | 19726677 |
| PMC | PMC2781590 |
| MeSH | Adaptor Proteins, Signal Transducing Adenosine Triphosphate / biosynthesis Carrier Proteins / physiology* Glycolysis Humans Hypoxia-Inducible Factor 1 / agonists Hypoxia-Inducible Factor 1 / metabolism Macrophages / metabolism* Mixed Function Oxygenases Protein Binding Protein Transport Repressor Proteins / antagonists & inhibitors Repressor Proteins / metabolism* |
| IF | 4.238 |
| Times Cited | 36 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pENTR Mint3/APBA3 (RDB08028) |