The DOI matches its Crossref record; 54 of the 55 references it cites were found in a registry or an index.
Carboxyl-Terminal Transactivation Activity of Hypoxia-Inducible Factor 1α Is Governed by a von Hippel-Lindau Protein-Independent, Hydroxylation-Regulated Association with p300/CBP
Open accessAbstract
Hypoxia-inducible factor 1 complex (HIF-1) plays a pivotal role in oxygen homeostasis and adaptation to hypoxia. Its function is controlled by both the protein stability and the transactivation activity of its alpha subunit, HIF-1 alpha. Hydroxylation of at least two prolyl residues in the oxygen-dependent degradation domain of HIF-1 alpha regulates its interaction with the von Hippel-Lindau protein (VHL) that targets HIF-1 alpha for ubiquitination and proteasomal degradation. Several prolyl hydroxylases have been found to specifically hydroxylate HIF-1 alpha. In this report, we investigated possible roles of VHL and hydroxylases in the regulation of the transactivation activity of the C-terminal activating domain (CAD) of HIF-1 alpha. We demonstrate that regulation of the transactivation activity of HIF-1 alpha CAD also involves hydroxylase activity but does not require functional VHL. In addition, stimulation of the CAD activity by a hydroxylase inhibitor, hypoxia, and desferrioxamine was severely blocked by the adenoviral oncoprotein E1A but not by an E1A mutant defective in targeting p300/CBP. We further demonstrate that a hydroxylase inhibitor, hypoxia, and desferrioxamine promote the functional and physical interaction between HIF-1 alpha CAD and p300/CBP in vivo. Taken together, our data provide evidence that hypoxia-regulated stabilization and transcriptional stimulation of HIF-1 alpha function are regulated through partially overlapping but distinguishable pathways.
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“although regulation of the CAD by hydroxylation does not appear to require pVHL (Sang et al. 2002).”
From FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor (2002) · cites this paper as Sang et al. 2002
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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 · cited 2×
“The interaction between VHL and HIF-1 depends on the hydroxylation of proline residues (Pro-402 and Pro-564) in the oxygen-dependent degradation domain of HIF-1 ( 17 , 19, 29, 51).”
BackgroundEpstein, 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
Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene
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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
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
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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
Purification and Characterization of Hypoxia-inducible Factor 1
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Self-citation
Research works printed but not linked: 5
- 10.1016/S0021-9258(19)61441-9 · DOI
- Ryan H., 2000, Cancer Res., 60, 4010
- Sang N., 2002, Frontiers Biosci., 7, d407
- Yang H., 2001, Cell Growth Differ., 12, 447
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Cited by
Sorted by citations
Hypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,690
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Role of VHL Gene Mutation in Human Cancer
Kim, W. Y., & Kaelin, W. G. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.061 · Cited by 953
Hypoxia-induced neutrophil survival is mediated by HIF-1α–dependent NF-κB activity
Walmsley, S. R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R. S., Cramer, T., Sobolewski, A., Condliffe, A. M., Cowburn, A. S., Johnson, N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040624 · Cited by 891
Metadata
- Authors
- Sang, N., Fang, J., Srinivas, V., Leshchinsky, I., & Caro, J.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Caro, Jaime
- ORCID
- Sang, Nianli
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2002-05-01
- Volume
- 22
- Issue
- 9
- Pages
- 2984-2992
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC133771
- OpenAlex
- W2121895466
- Cited by
- 143
- References
- 55
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Fudan University
- Huashan Hospital
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007821)
- National Cancer Institute (R01CA089212, R01CA89212-02)
- 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, prolyl hydroxylase, von Hippel-Lindau protein, CBP/p300, deferoxamine, hypoxia, oxygen homeostasis, transcriptional regulation, protein stability
- MeSH terms
- Hypoxia, Aspartate Carbamoyltransferase, Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing), Cell Line, Deferoxamine, Dihydroorotase, DNA-Binding Proteins, HeLa Cells, Humans, Mixed Function Oxygenases, Hydroxylation, Ligases, Multienzyme Complexes, Nuclear Proteins, Protein Binding, Transcription Factors, Blotting, Western, Transcriptional Activation, Trans-Activators, Adenovirus E1A Proteins, Protein Isoforms, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Hypoxia-Inducible Factor 1, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit
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