PMID- 10202154
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20181201
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 7
DP  - 1999 Apr 1
TI  - Molecular mechanisms of transcription activation by HLF and HIF1alpha in response
      to hypoxia: their stabilization and redox signal-induced interaction with
      CBP/p300.
PG  - 1905-14
AB  - Hypoxia-inducible factor 1 alpha (HIF1alpha) and its related factor, HLF,
      activate expression of a group of genes such as erythropoietin in response to low
      oxygen. Transfection analysis using fusion genes of GAL4DBD with various
      fragments of the two factors delineated two transcription activation domains
      which are inducible in response to hypoxia and are localized in the C-terminal
      half. Their sequences are conserved between HLF and HIF1alpha. One is designated 
      NAD (N-terminal activation domain), while the other is CAD (C-terminal activation
      domain). Immunoblot analysis revealed that NADs, which were rarely detectable at 
      normoxia, became stabilized and accumulated at hypoxia, whereas CADs were
      constitutively expressed. In the mammalian two-hybrid system, CAD and NAD baits
      enhanced the luciferase expression from a reporter gene by co-transfection with
      CREB-binding protein (CBP) prey, whereas CAD, but not NAD, enhanced
      beta-galactosidase expression in yeast by CBP co-expression, suggesting that NAD 
      and CAD interact with CBP/p300 by a different mechanism. Co-transfection
      experiments revealed that expression of Ref-1 and thioredoxin further enhanced
      the luciferase activity expressed by CAD, but not by NAD. Amino acid replacement 
      in the sequences of CADs revealed a specific cysteine to be essential for their
      hypoxia-inducible interaction with CBP. Nuclear translocation of thioredoxin from
      cytoplasm was observed upon reducing O2 concentrations.
FAU - Ema, M
AU  - Ema M
AD  - Department of Chemistry, Graduate School of Science, Tohoku University, Sendai
      980-77, Japan.
FAU - Hirota, K
AU  - Hirota K
FAU - Mimura, J
AU  - Mimura J
FAU - Abe, H
AU  - Abe H
FAU - Yodoi, J
AU  - Yodoi J
FAU - Sogawa, K
AU  - Sogawa K
FAU - Poellinger, L
AU  - Poellinger L
FAU - Fujii-Kuriyama, Y
AU  - Fujii-Kuriyama Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA Primers)
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 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 4.2.- (Carbon-Oxygen Lyases)
RN  - EC 4.2.99.18 (APEX1 protein, human)
RN  - EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Carbon-Oxygen Lyases/metabolism
MH  - Cell Hypoxia/*genetics/*physiology
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - *DNA-(Apurinic or Apyrimidinic Site) Lyase
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Drug Stability
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Oxidation-Reduction
MH  - Signal Transduction
MH  - Thioredoxins/metabolism
MH  - Trans-Activators/genetics/*metabolism
MH  - *Transcription Factors
MH  - *Transcriptional Activation
MH  - Transfection
PMC - PMC1171276
EDAT- 1999/04/15 00:00
MHDA- 1999/04/15 00:01
CRDT- 1999/04/15 00:00
PHST- 1999/04/15 00:00 [pubmed]
PHST- 1999/04/15 00:01 [medline]
PHST- 1999/04/15 00:00 [entrez]
AID - 10.1093/emboj/18.7.1905 [doi]
PST - ppublish
SO  - EMBO J. 1999 Apr 1;18(7):1905-14. doi: 10.1093/emboj/18.7.1905.