PMID- 20663879
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 39
DP  - 2010 Sep 24
TI  - A membrane protease regulates energy production in macrophages by activating 
      hypoxia-inducible factor-1 via a non-proteolytic mechanism.
PG  - 29951-64
LID - 10.1074/jbc.M110.132704 [doi]
AB  - Most cells produce ATP in the mitochondria by oxidative phosphorylation. However, 
      macrophages, which are major players in the innate immune system, use aerobic 
      glycolysis to produce ATP. HIF-1 (hypoxia-inducible factor-1) regulates 
      expression of glycolysis-related genes and maintains macrophage glycolytic 
      activity. However, it is unclear how HIF-1 activity is maintained in macrophages 
      during normoxia. In this study, we found that macrophages lacking membrane type 1 
      matrix metalloproteinase (MT1-MMP/MMP-14), a potent invasion-promoting protease, 
      exhibited considerably lower ATP levels than wild-type cells. HIF-1 was activated 
      by an unanticipated function of MT1-MMP, which led to the stimulation of ATP 
      production via glycolysis. The cytoplasmic tail of MT1-MMP bound to FIH-1 (factor 
      inhibiting HIF-1), which led to the inhibition of the latter by its recently 
      identified inhibitor, Mint3/APBA3. We have thus identified a new function of 
      MT1-MMP to mediate production of ATP so as to support energy-dependent macrophage 
      functions by a previously unknown non-proteolytic mechanism.
FAU - Sakamoto, Takeharu
AU  - Sakamoto T
AD  - Division of Cancer Cell Research, Institute of Medical Science, University of 
      Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
FAU - Seiki, Motoharu
AU  - Seiki M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100727
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 (Apba3 protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Mmp14 protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Repressor Proteins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.- (factor inhibiting hypoxia-inducible factor 1, mouse)
RN  - EC 1.14.11.- (HIF1AN protein, human)
RN  - EC 3.4.24.80 (MMP14 protein, human)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adenosine Triphosphate/genetics/*metabolism
MH  - Animals
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Line
MH  - Gene Expression Regulation/*physiology
MH  - Glycolysis/*physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Macrophages/*metabolism
MH  - Matrix Metalloproteinase 14/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mixed Function Oxygenases/genetics/metabolism
MH  - Proteins/genetics/metabolism
MH  - Repressor Proteins/genetics/metabolism
PMC - PMC2943292
EDAT- 2010/07/29 06:00
MHDA- 2010/10/22 06:00
PMCR- 2011/09/24
CRDT- 2010/07/29 06:00
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
PHST- 2011/09/24 00:00 [pmc-release]
AID - S0021-9258(19)89031-2 [pii]
AID - M110.132704 [pii]
AID - 10.1074/jbc.M110.132704 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Sep 24;285(39):29951-64. doi: 10.1074/jbc.M110.132704. Epub 
      2010 Jul 27.