Cited by 2,113Cancer, Hypoxia, and MetabolismErythropoietin and Anemia TreatmentUbiquitin and proteasome pathways

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Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway

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Huang, L. Eric, Gu, Jie, Schau, Maureen, Bunn, H. Franklin·1998·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.95.14.7987PMC PMC20916

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Abstract

Hypoxia induces a group of physiologically important genes such as erythropoietin and vascular endothelial growth factor. These genes are transcriptionally up-regulated by hypoxia-inducible factor 1 (HIF-1), a global regulator that belongs to the basic helix-loop-helix PAS family. Although HIF-1 is a heterodimer composed of α and β subunits, its activity is primarily determined by hypoxia-induced stabilization of HIF-1α, which is otherwise rapidly degraded in oxygenated cells. We report the identification of an oxygen-dependent degradation (ODD) domain within HIF-1α that controls its degradation by the ubiquitin-proteasome pathway. The ODD domain consists of ≈200 amino acid residues, located in the central region of HIF-1α. Because portions of the domain independently confer degradation of HIF-1α, deletion of this entire region is required to give rise to a stable HIF-1α, capable of heterodimerization, DNA-binding, and transactivation in the absence of hypoxic signaling. Conversely, the ODD domain alone confers oxygen-dependent instability when fused to a stable protein, Gal4. Hence, the ODD domain plays a pivotal role for regulating HIF-1 activity and thereby may provide a means of controlling gene expression by changes in oxygen tension.

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Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
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
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A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Amino Acid Sequences Common to Rapidly Degraded Proteins: The PEST Hypothesis
Rogers, S. W., Wells, R., & Rechsteiner, M. (1986) · Science · doi:10.1126/science.2876518 · Cited by 2,541
Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.
Rock, K. L., Gramm, C., Rothstein, L., Clark, K., Stein, R., Dick, L., Hwang, D., & Goldberg, A. L. (1994) · Cell · doi:10.1016/s0092-8674(94)90462-6 · Cited by 2,524
STRUCTURE AND FUNCTIONS OF THE 20S AND 26S PROTEASOMES
Coux, O., Tanaka, K., & Goldberg, A. L. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.004101 · Cited by 2,438
The ubiquitin-proteasome proteolytic pathway
Ciechanover, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90396-4 · Cited by 1,804
PEST sequences and regulation by proteolysis
Rechsteiner, M., & Rogers, S. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10031-1 · Cited by 1,707
Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions
Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674
The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649

Show all 40 references

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10.1128/mcb.12.12.5447-5454.1992 · DOI · Paper page
10.1128/mcb.14.9.6075-6086.1994 · DOI

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Morel, Y., & Barouki, R. (1999) · Biochemical Journal · doi:10.1042/bj3420481 · Cited by 555
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Treins, C., Giorgetti‐Peraldi, S., Murdaca, J., Semenza, G. L., & OBBERGHEN, E. V. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204152200 · Cited by 554
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Wan, C., Gilbert, S. R., Wang, Y., Cao, X., Shen, X., Ramaswamy, G., Jacobsen, K. A., Al-Aql, Z. S., Eberhardt, A. W., Gerstenfeld, L. C., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708474105 · Cited by 528
Induction of HIF–1α in response to hypoxia is instantaneous
Jewell, U. R., Kvietikova, I., Scheid, A., Bauer, C., Wenger, R. H., & Gassmann, M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0732fje · Cited by 567
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Hochachka, P. W., & Lutz, P. L. (2001) · Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology · doi:10.1016/s1096-4959(01)00408-0 · Cited by 500
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Schwartz, A. L., & Ciechanover, A. J. (2008) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.051208.165340 · Cited by 498
Cartilage engineering: a crucial combination of cells, biomaterials and biofactors
Vinatier, C. S., Mrugala, D., Jørgensen, C., Guicheux, J., & Noël, D. (2009) · Trends in biotechnology · doi:10.1016/j.tibtech.2009.02.005 · Cited by 501
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Kung, A. L., Zabludoff, S. D., France, D. S., Freedman, S. J., Tanner, E. A., Vieira, A., Cornell-Kennon, S., Lee, J., Wang, B., Wang, J., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.009 · Cited by 480
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Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter, K. C., & Harris, A. L. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2018 · Cited by 478
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Liu, Y. V., Baek, J. H., Zhang, H., Diez, R., Cole, R. N., & Semenza, G. L. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.01.001 · Cited by 490
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Yeo, E., Chun, Y., Cho, Y.-S., Kim, J., Lee, J.-C., Kim, M.-S., & Park, J.-W. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.7.516 · Cited by 479
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Stowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471
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Le, Q., Denko, N. C., & Giaccia, A. J. (2004) · Cancer and Metastasis Reviews · doi:10.1023/b:canc.0000031768.89246.d7 · Cited by 467
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Semenza, G. L. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.11.009 · Cited by 469
Proline hydroxylation and gene expression
Kaelin, W. G. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133142 · Cited by 468
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Hirota, K., & Semenza, G. L. (2006) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.12.003 · Cited by 473
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Tsatsaris, V., Goffin, F., Munaut, C., Brichant, J.-F., Pignon, M.-R., Noël, A., Schaaps, J., CABROL, D., Frankenne, F., & Foidart, J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030528 · Cited by 465

Authors: Huang, L. E., Gu, J., Schau, M., & Bunn, H. F.
Affiliations: Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
Brigham and Women's Hospital (US)
ORCID: Gu, Jie
Bunn, H. Franklin
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1998-07-07
Volume: 95
Issue: 14
Pages: 7987-7992
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.95.14.7987
PMC: PMC20916
OpenAlex: W2075054245
Cited by: 2,113
References: 40
Citations by year: 2026: 36 · 2025: 36 · 2024: 39 · 2023: 43 · 2022: 49 · 2021: 56 · 2020: 49 · 2019: 60 · 2018: 59 · 2017: 56 · 2016: 70 · 2015: 65 · 2014: 78 · 2013: 92 · 2012: 74
FWCI: 28.30
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK041234, R0-DK41234, F32-DK09365, F32DK009365)
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 › Ubiquitin and proteasome pathways
Keywords: hypoxia-inducible factor-1α, oxygen-dependent degradation domain, ubiquitin-proteasome system, protein degradation, hypoxia, oxygen sensing, transcriptional regulation, erythropoietin, vascular endothelial growth factor
MeSH terms: Animals, Cell Line, Cysteine Endopeptidases, DNA, DNA-Binding Proteins, Multienzyme Complexes, Nuclear Proteins, Oxygen, Protein Binding, Transcription Factors, Ubiquitins, Signal Transduction, Cell Hypoxia, Dimerization, Proteasome Endopeptidase Complex, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit

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Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway

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