PMID- 15611046
OWN - NLM
STAT- MEDLINE
DCOM- 20050408
LR  - 20220318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 8
DP  - 2005 Feb 25
TI  - Hypoxia-enhanced expression of the proprotein convertase furin is mediated by 
      hypoxia-inducible factor-1: impact on the bioactivation of proproteins.
PG  - 6561-9
AB  - Hypoxia is a common tumorigenesis enhancer, mostly owing to its impact on gene 
      expression of many angiogenic and invasion-related mediators, some of which are 
      natural substrates for the proprotein convertase furin. Analysis of furin 
      promoters revealed the presence of putative binding sites for hypoxia-inducible 
      factor-1 (HIF-1), a transcription complex that plays a pivotal role in cellular 
      adaptation to hypoxia. In fact, we demonstrate herein that the levels of fur 
      mRNA, encoding furin, are remarkably increased upon hypoxic challenge. 
      Cotransfection of a HIF-1alpha dominant negative form in wild-type (WT) cells or 
      transfection of a furin promoter-reporter gene in HIF-1-deficient cells indicated 
      the requirement of HIF-1 for furin promoter activation by hypoxia. Direct HIF-1 
      action on the furin promoter was identified as a canonical hypoxia-responsive 
      element site with enhancer capability. The hypoxic/HIF-1 regulation of furin 
      correlated with an increased proteolytic activation of the substrates 
      membrane-type 1 matrix metalloproteinase and transforming growth factor-beta1. 
      Our findings unveil a new facet of the physiological consequences of 
      hypoxia/HIF-1, through enhanced furin-induced proteolytic processing/activation 
      of proproteins known to be involved in tumorigenesis.
FAU - McMahon, Stephanie
AU  - McMahon S
AD  - Immunology Division, Pulmonary Division, Faculty of Medicine, Universite de 
      Sherbrooke, Sherbrooke, Quebec.
FAU - Grondin, Francine
AU  - Grondin F
FAU - McDonald, Patrick P
AU  - McDonald PP
FAU - Richard, Darren E
AU  - Richard DE
FAU - Dubois, Claire M
AU  - Dubois CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041215
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.4.21.- (Proprotein Convertases)
RN  - EC 3.4.21.75 (Furin)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Binding Sites
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/*physiology
MH  - Furin/*genetics
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Hypoxia/*genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Matrix Metalloproteinase 1/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Nuclear Proteins/*physiology
MH  - Promoter Regions, Genetic
MH  - Proprotein Convertases/genetics
MH  - RNA, Messenger/analysis
MH  - Transcription Factors/genetics/*physiology
MH  - Transcriptional Activation
MH  - Transfection
MH  - Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2004/12/22 09:00
MHDA- 2005/04/09 09:00
CRDT- 2004/12/22 09:00
PHST- 2004/12/22 09:00 [pubmed]
PHST- 2005/04/09 09:00 [medline]
PHST- 2004/12/22 09:00 [entrez]
AID - S0021-9258(19)62767-5 [pii]
AID - 10.1074/jbc.M413248200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Feb 25;280(8):6561-9. doi: 10.1074/jbc.M413248200. Epub 2004 
      Dec 15.