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Cited by 629Cancer, Hypoxia, and MetabolismErythropoietin and Anemia TreatmentKruppel-like factors research

Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α

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Jiang, Bing-Hua, Zheng, Jenny Z., Leung, Sandra W., Roe, Rick, Semenza, Gregg L.·1997·Journal of Biological Chemistry
DOI 10.1074/jbc.272.31.19253
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Abstract

Hypoxia-inducible factor 1 (HIF-1) binds to cis-acting hypoxia-response elements within the erythropoietin, vascular endothelial growth factor, and other genes to activate transcription in hypoxic cells. HIF-1 is a basic helix-loop-helix transcription factor composed of HIF-1alpha and HIF-1beta subunits. Here, we demonstrate that HIF-1alpha contains two transactivation domains located between amino acids 531 and 826. When expressed as GAL4 fusion proteins, the transcriptional activity of these domains increased in response to hypoxia. Fusion protein levels were unaffected by changes in cellular O2 tension. Two minimal transactivation domains were localized to amino acid residues 531-575 and 786-826. The transcriptional activation domains were separated by amino acid sequences that inhibited transactivation. Deletion analysis demonstrated that the gradual removal of inhibitory domain sequences (amino acids 576-785) was associated with progressively increased transcriptional activity of the fusion proteins, especially in cells cultured at 20% O2. Transcriptional activity of GAL4/HIF-1alpha fusion proteins was increased in cells exposed to 1% O2, cobalt chloride, or desferrioxamine, each of which also increased levels of endogenous HIF-1alpha protein but did not affect fusion protein levels. These results indicate that increased transcriptional activity mediated by HIF-1 in hypoxic cells results from both increased HIF-1alpha protein levels and increased activity of HIF-1alpha transactivation domains.

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Crossref · 10.1074/jbc.272.31.19253

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  • PKM2-V5 mainly binds to GST-HIF-1α (575-786), which encodes an inhibitory domain associated with regulation of the HIF-1α transactivation domain.

    “We further mapped PKM2 binding within the transactivation domain of HIF-1α and found that PKM2-V5 mainly bound to GST-HIF-1α (575–786) (Figure 2E), which encodes an inhibitory domain associated with regulation of the HIF-1α transactivation domain (Jiang et al., 1997).”

    From Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1 (2011) · cites this paper as Jiang et al., 1997

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Authors
Jiang, B.-H., Zheng, J. Z., Leung, S. W., Roe, R., & Semenza, G. L.
Affiliations
Johns Hopkins University (US)
Corresponding author
Semenza, Gregg L.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-08
Volume
272
Issue
31
Pages
19253-19260
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.272.31.19253
OpenAlex
W2005613270
Cited by
629
References
45
Citations by year
2026: 13 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 23 · 2021: 22 · 2020: 14 · 2019: 20 · 2018: 16 · 2017: 10 · 2016: 23 · 2015: 17 · 2014: 24 · 2013: 24 · 2012: 18
FWCI
8.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk039869-16)
  • National Heart, Lung, and Blood Institute (R01HL55338, R01HL055338)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK39869)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Keywords
hypoxia-inducible factor-1α, HIF-1, transactivation domain, inhibitory domain, transcriptional activation, hypoxia response, hypoxia response element, bHLH transcription factors, ARNT, cobalt chloride, deferoxamine, oxygen partial pressure, erythropoietin, vascular endothelial growth factor
MeSH terms
Animals, Hypoxia, DNA-Binding Proteins, Erythropoietin, Lymphokines, Nuclear Proteins, Oxygen, Peptide Fragments, Transcription Factors, Transcriptional Activation, Endothelial Growth Factors, Genes, Reporter, Helix-Loop-Helix Motifs, COS Cells, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit

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