The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Hsp70 and CHIP Selectively Mediate Ubiquitination and Degradation of Hypoxia-inducible Factor (HIF)-1α but Not HIF-2α
Open accessAbstract
Hypoxia-inducible factors (HIFs) are transcription factors that mediate adaptive responses to reduced oxygen availability. HIF-alpha subunits are stabilized under conditions of acute hypoxia. However, prolonged hypoxia leads to decay of HIF-1alpha but not HIF-2alpha protein levels by unknown mechanisms. Here, we identify Hsp70 and CHIP (carboxyl terminus of Hsc70-interacting protein) as HIF-1alpha-interacting proteins. Hsp70, through recruiting the ubiquitin ligase CHIP, promotes the ubiquitination and proteasomal degradation of HIF-1alpha but not HIF-2alpha, thereby inhibiting HIF-1-dependent gene expression. Disruption of Hsp70-CHIP interaction blocks HIF-1alpha degradation mediated by Hsp70 and CHIP. Inhibition of Hsp70 or CHIP synthesis by RNA interference increases protein levels of HIF-1alpha but not HIF-2alpha and attenuates the decay of HIF-1alpha levels during prolonged hypoxia. Thus, Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of HIF-1alpha but not HIF-2alpha protein.
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“A stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic screen (Luo et al., 2010) revealed that PKM2 preferentially bound to a GST-HIF-1α (531–826) fusion protein containing amino acid residues 531–826 of HIF-1α as compared to GST alone (Figure 2A), suggesting that PKM2 is a novel HIF-1α-interacting protein.”
From Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1 (2011) · cites this paper as Luo et al., 2010
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Cites
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
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
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574
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
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
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
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251
Hsp70 chaperones: Cellular functions and molecular mechanism
Mayer, M. P., & Bukau, B. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4464-6 · Cited by 2,857
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Research works printed but not linked: 2
- Semenza, 1992, Mol. Cell. Biol., 12, 5447
- Gu, 1998, Gene Expr., 7, 205
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Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1
Luo, W., Hu, H., Chang, R., Zhong, J., Knabel, M., O'Meally, R., Cole, R. N., Pandey, A., & Semenza, G. L. (2011) · Cell · doi:10.1016/j.cell.2011.03.054 · Cited by 1,463
Transcriptional regulation by hypoxia inducible factors
Dengler, V. L., Galbraith, M. D., & Espinosa, J. M. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.838205 · Cited by 816
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641
Metadata
- Authors
- Luo, W., Zhong, J., Chang, R., Hu, H., Pandey, A., & Semenza, G. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Semenza, Gregg L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 285
- Issue
- 6
- Pages
- 3651-3663
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2823506
- OpenAlex
- W2022643257
- Cited by
- 232
- References
- 39
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 15 · 2023: 12 · 2022: 12 · 2021: 11 · 2020: 16 · 2019: 18 · 2018: 10 · 2017: 18 · 2016: 15 · 2015: 22 · 2014: 11 · 2013: 19 · 2012: 15
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health (n01hv28180-13-0-0, RR020839)
- National Heart, Lung, and Blood Institute (N01 HV-28180, N01 HV028180)
- National Center for Research Resources (U54RR020839)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- HSP70, CHIP, HIF-1α, HIF-2α, hypoxia-inducible factor, ubiquitination, proteasomal degradation, protein stability, prolonged hypoxia, ubiquitin ligase
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Cell Line, Humans, Mutation, Protein Binding, Transfection, Immunoblotting, Cell Hypoxia, HSP70 Heat-Shock Proteins, RNA Interference, Ubiquitin-Protein Ligases, Cell Line, Tumor, Proteasome Endopeptidase Complex, Immunoprecipitation, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Ubiquitination
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