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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- Semenza, 1992, Mol. Cell. Biol., 12, 5447
- Gu, 1998, Gene Expr., 7, 205
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Phosphorylated Hsp70-CHIP BLItz Data
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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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