The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Sumoylation increases HIF-1α stability and its transcriptional activity
Abstract
HIF-1 is closely involved in various biological processes, including angiogenesis, energy metabolism, and cell survival. HIF-1 consists of an oxygen-sensitive HIF-1alpha and oxygen-insensitive HIF-1beta. Oxygen-sensitive HIF-1alpha is subjected to post-translational modifications such as hydroxylation, ubiquitination, and acetylation, which are related to the regulation of its stability. In this present study, we found that the ectopic expression of SUMO-1 increased HIF-1alpha stability by the co-transfection study with HIF-1alpha and SUMO-1. Furthermore, the ectopic expression of SUMO-1 enhanced the transcriptional activity of HIF-1alpha. In the subsequent immunoprecipitation assay, SUMO-1 was co-immunoprecipitated with HIF-1alpha, implying that HIF-1alpha is covalently modified by SUMO-1. Thereafter, using a series of lysine mutants in the ODD domain, we found that HIF-1alpha was sumoylated at Lys(391) and Lys(477), suggesting that sumoylation at these two lysine residues enhances HIF-1alpha stability by possibly modulating other post-translational modifications. Altogether, we demonstrate that HIF-1alpha is upregulated through SUMO-1 modification at Lys(391)/Lys(477) residues, which may stabilize HIF-1alpha and enhance its transcriptional activity.
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“Because SUMOylation enhances both the stability and transcriptional activity of HIF-1α [190], altered SUMO conjugation may contribute to reduced HIF-1α protein levels.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [190]
In the citing paper
“Because SUMOylation enhances both the stability and transcriptional activity of HIF-1α [190], altered SUMO conjugation may contribute to reduced HIF-1α protein levels.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [190]
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Metadata
- Authors
- Bae, S.-H., Jeong, J.-W., Park, J. A., Kim, S.-H., Bae, M.-K., Choi, S.-J., & Kim, K.-W.
- Affiliations
- Seoul National University (KR)
- Harvard University (US)
- Pusan National University (KR)
- Corresponding author
- Kim, Kyu-Won
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 324
- Issue
- 1
- Pages
- 394-400
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2085483520
- Cited by
- 232
- References
- 26
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 15 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 12 · 2012: 8
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- HIF-1α, SUMOylation, SUMO1, protein stability, transcriptional activity, lysine modification, post-translational modification, ARNT, oxygen sensing, lysine mutants
- MeSH terms
- Amino Acid Sequence, Animals, Enzyme Stability, HeLa Cells, Humans, Lysine, Molecular Sequence Data, Protein Processing, Post-Translational, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Enzymologic, SUMO-1 Protein, Hypoxia-Inducible Factor 1, alpha Subunit
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