PMID- 8900415
OWN - NLM
STAT- MEDLINE
DCOM- 19961216
LR  - 20131121
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 334
IP  - 2
DP  - 1996 Oct 15
TI  - Absolute requirement of aryl hydrocarbon receptor nuclear translocator protein 
      for gene activation by hypoxia.
PG  - 389-94
AB  - Hypoxia-inducible factor 1 (HIF-1) is a DNA-binding heterodimeric protein complex 
      originally described in the transcriptional activation of the erythropoietin gene 
      by hypoxia. This protein complex is composed of two subunits, HIF-1alpha and 
      -1beta (aryl hydrocarbon receptor nuclear translocator, ARNT). In this study, we 
      used ARNT-deficient cells, derived from the mouse hepatoma cell line Hepa1c1c7, 
      to further characterize HIF-1 complex formation and its relationship with gene 
      activation by hypoxia and desferrioxamine (Df). Gel shift assays revealed that 
      ARNT is absolutely required for the formation of the HIF-1 DNA-binding complex. 
      Results from RNase protection assays and Northern blots showed that the lack of 
      functional HIF-1 complex completely abrogated the response to hypoxia of vascular 
      endothelial growth factor (VEGF) and the glycolytic enzymes aldolase A (ALDA) and 
      phosphoglycerate kinase 1 (PGK-1), genes known to be upregulated by low oxygen 
      tension. Desferrioxamine induction of VEGF and PGK-1 genes was reduced in the 
      ARNT-deficient cells, but at difference with hypoxia, it was not completely 
      suppressed. These results suggest that Df is able to activate gene transcription 
      through HIF-1-independent mechanisms. Exposure to hypoxia or Df did not induce 
      any changes in HIF-1alpha and -1beta mRNA levels, suggesting that 
      posttranscriptional mechanisms are involved in HIF-1 complex activation.
FAU - Salceda, S
AU  - Salceda S
AD  - Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson 
      Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, 
      USA.
FAU - Beck, I
AU  - Beck I
FAU - Caro, J
AU  - Caro J
LA  - eng
GR  - 1 F32 HL 09247/HL/NHLBI NIH HHS/United States
GR  - DK-34642/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Actins)
RN  - 0 (Arnt protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - EC 2.7.2.3 (Phosphoglycerate Kinase)
RN  - EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Actins/biosynthesis
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator
MH  - Blotting, Northern
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Deferoxamine/pharmacology
MH  - Endothelial Growth Factors/biosynthesis
MH  - Fructose-Bisphosphate Aldolase/biosynthesis
MH  - *Gene Expression Regulation, Neoplastic/drug effects
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Liver Neoplasms, Experimental
MH  - Lymphokines/biosynthesis
MH  - Mice
MH  - Nuclear Proteins/*metabolism
MH  - Phosphoglycerate Kinase/biosynthesis
MH  - Receptors, Aryl Hydrocarbon/*biosynthesis
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1996/10/15 00:00
MHDA- 1996/10/15 00:01
CRDT- 1996/10/15 00:00
PHST- 1996/10/15 00:00 [pubmed]
PHST- 1996/10/15 00:01 [medline]
PHST- 1996/10/15 00:00 [entrez]
AID - S0003-9861(96)90469-5 [pii]
AID - 10.1006/abbi.1996.0469 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1996 Oct 15;334(2):389-94. doi: 10.1006/abbi.1996.0469.