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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Cites
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
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The Expression and Function of PPAR and HIF-1 in Human Melanoma
Mills, C. N. (2007)
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Zheng, X. (2009) · Figshare
Hypoxia-induced phenotypic modulation of human neuroblastoma cells
Mengelbier, L. H. (2006) · Lund University Publications (Lund University)
Hong, I., Seo, H., Lee, M., Kim, J., Chung, J., Lee, B., & Lee, M. (2007) · Toxicological Research · doi:10.5487/tr.2007.23.3.231
The novel sumoylation enhancer RSUME is implicated in pituitary tumour pathogenesis
Shan, B. (2010) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0030-1266992
Mechanisms of chronic complications of diabetes with focus on mitochondria and oxygen sensing
Savu, I. O. (2009) · Figshare
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Hale, S. A. (2008) · ScholarWorks -A service of University of Vermont Libraries (University of Vermont)
Novel Functions of ErbB4 and NRG-1 in Development and Cancer
Paatero, I. (2013) · UTUPub (University of Turku)
Signorini, L. (2015) · Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · doi:10.13130/signorini-lucia_phd2015-12-16
Étude de la SUMOylation dans l’immunité innée et l’oncogenèse
Decque, A. (2014) · theses.fr (ABES) · doi:10.70675/9c751457z588az4210za1bbz3b5d58fb2087
Mammalian O2 Sensing and Signalling
Chaplin, V. D., Barlow, A. N., & Knapp, M. J. (2017) · Royal Society of Chemistry eBooks · doi:10.1039/9781788012836-00219
Zhao, F. L. (2014) · UA Campus Repository (The University of Arizona)
Atta, W. O., & Azeiz, A. Z. A. (2021) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2021.98006
Sâmbrian, O. A. (2010) · Dialnet (Universidad de la Rioja)
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Lin, I., Chang, K., Cheng, F., Kanwar, R. K., Kamplikar, P., Kanwar, J. R., & Cheung, C. H. A. (2025) · Springer eBooks · doi:10.1007/978-981-96-1016-7_11
Tumor Hypoxia: An Introduction
Ray, S. K., & Mukherjee, S. (2025) · Springer eBooks · doi:10.1007/978-981-96-1016-7_1
Oxygen-dependent regulation of the activating transcription factor-4 (ATF-4)
Wottawa, M. (2010) · eDiss (Georg-August-Universität Göttingen)
Guerrab, A. E. (2011) · theses.fr (ABES) · doi:10.70675/0680d6aez5ddfz48efzabe9zf58f93e15842
Impact du ciblage du domaine de liaison de HIF-1α avec HIF-1β sur le paysage immunitaire du mélanome
Lequeux, A. (2020) · theses.fr (ABES) · doi:10.70675/a29d12dbz79c1z4d37za978z2e2319131c82
ROS–SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health
Na, A., Lee, H., & Ryu, H. (2026) · Antioxidants · doi:10.3390/antiox15040453
Sefa, S. M., Sarkar, J., Robin, A. H. K., & Uddin, M. (2026) · PLoS ONE · doi:10.1371/journal.pone.0348861
Song, Y., Li, Z., Yuan, L., Li, Z., Lai, F., & Xiao, W. (2026) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2026.112062
Lu, J., Chen, X., Chen, Y., Wang, D., Wu, J., Jin, R., Guo, H., Zhang, Q., Zhao, P., Shi, Y., et al. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108417
Kanamaluru, D. (2011) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Covalent Protein Modification as a Mechanism for Dynamic Recruitment of Specific Interactors
Bertos, N., Sangwan, V., Yang, X., & Park, M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-6382-6_11
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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