Cited by 234Cancer, Hypoxia, and MetabolismHeat shock proteins researchUbiquitin and proteasome pathways

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 access

Luo, Weibo, Zhong, Jun, Chang, Ryan, Hu, Hongxia, Pandey, Akhilesh, Semenza, Gregg L.·2010·Journal of Biological Chemistry

DOI 10.1074/jbc.m109.068577PMC PMC2823506

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.m109.068577

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
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
Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics
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
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
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
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

Flagged first, then by citations

Show all 39 references

Research works printed but not linked: 2

Semenza, 1992, Mol. Cell. Biol., 12, 5447
Gu, 1998, Gene Expr., 7, 205

Sorted by citations

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
Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641
Passing the baton: the HIF switch
Koh, M. Y., & Powis, G. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.06.004 · Cited by 589
The regulation of immune tolerance by FOXP3
Lu, L., Barbi, J., & Pan, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.75 · Cited by 580
HIF-1 and HIF-2 Transcription Factors - Similar but Not Identical
Loboda, A., Jozkowicz, A., & Dulak, J. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0067-2 · Cited by 477
Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms
Korbecki, J., Simińska, D., Gąssowska-Dobrowolska, M., Listos, J., Gutowska, I., Chlubek, D., & Baranowska‐Bosiacka, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910701 · Cited by 401
The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy
Albadari, N. G., Deng, S., & Li, W. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1613370 · Cited by 365
The Hypoxia-Associated Factor Switches Cells from HIF-1α- to HIF-2α-Dependent Signaling Promoting Stem Cell Characteristics, Aggressive Tumor Growth and Invasion
Koh, M. Y., Lemos, R., Liu, X., & Powis, G. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4142 · Cited by 350
The Ubiquitin Ligase Stub1 Negatively Modulates Regulatory T Cell Suppressive Activity by Promoting Degradation of the Transcription Factor Foxp3
Chen, Z., Barbi, J. J., Bu, S., Yang, H., Li, Z., Gao, Y., Jinasena, D., Fu, J. L., Lin, F., Chen, C., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.006 · Cited by 300
Regulation of cell proliferation by hypoxia-inducible factors
Hubbi, M. E., & Semenza, G. L. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00279.2015 · Cited by 311
miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target
Serocki, M., Bartoszewska, S., Janaszak-Jasiecka, A., Ochocka, R. J., Collawn, J. F., & Bartoszewski, R. (2018) · Angiogenesis · doi:10.1007/s10456-018-9600-2 · Cited by 288
Reprogramming of the Tumor in the Hypoxic Niche: The Emerging Concept and Associated Therapeutic Strategies
Qiu, G., Jin, M., Dai, J., Sun, W., Feng, J., & Jin, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.002 · Cited by 250
Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation
Hubbi, M. E., Hu, H., Gupta, K., Ahmed, I., Levchenko, A., & Semenza, G. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.414771 · Cited by 246
DUBs, Hypoxia, and Cancer
Mennerich, D., Kubaichuk, K. I., & Kietzmann, T. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.08.005 · Cited by 234
Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression
Luo, W., Chang, R., Zhong, J., Pandey, A., & Semenza, G. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217394109 · Cited by 228
Self-citation
Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression
Saxena, K., & Jolly, M. K. (2019) · Biomolecules · doi:10.3390/biom9080339 · Cited by 223
Understanding Command and Control
Alberts, D. S., & Hayes, R. E. (2006) · Defense Technical Information Center (DTIC) · Cited by 219
Metabolic control of the Treg/Th17 axis
Barbi, J. J., Pardoll, D. M., & Pan, F. (2013) · Immunological Reviews · doi:10.1111/imr.12029 · Cited by 227
Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment
Wu, P., Gao, W. Q., Su, M., Nice, E. C., Zhang, W., Lin, J., & Xie, N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641469 · Cited by 218
Primary endothelial cell–specific regulation of hypoxia‐inducible factor (HIF)‐1 and HIF‐2 and their target gene expression profiles during hypoxia
Bartoszewski, R., Moszyńska, A., Serocki, M., Cabaj, A., Polten, A., Ochocka, R., Dell'Italia, L., Bartoszewska, S., Króliczewski, J., Dąbrowski, M., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201802650rr · Cited by 199
HDAC4 Protein Regulates HIF1α Protein Lysine Acetylation and Cancer Cell Response to Hypoxia
Geng, H., Harvey, C. T., Pittsenbarger, J., Liu, Q., Beer, T. M., Xue, C., & Qian, D. Z. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257055 · Cited by 197
Heat Shock Proteins: Cell Protection through Protein Triage
Lanneau, D., Wettstein, G., Bonniaud, P., & Garrido, C. (2010) · The Scientific World JOURNAL · doi:10.1100/tsw.2010.152 · Cited by 191
STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy
Ferreira, J. V., Fofo, H., Bejarano, E., Bento, C. F., Ramalho, J. S., Girão, H., & Pereira, P. (2013) · Autophagy · doi:10.4161/auto.25190 · Cited by 186
NQO1 inhibits proteasome-mediated degradation of HIF-1α
Oh, E., Kim, J., Kim, J. M., Kim, S., Lee, J., Hong, S., Goodwin, J., Ruthenborg, R. J., Jung, M. G., Lee, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms13593 · Cited by 178
Hypoxia Induces Drug Resistance in Colorectal Cancer through the HIF-1α/miR-338-5p/IL-6 Feedback Loop
Xu, K., Zhan, Y., Yuan, Z., Qiu, Y., Wang, H., Fan, G., Wang, J., Li, W., Cao, Y., Shen, X., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.05.017 · Cited by 160
Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes
Bento, C. F., & Pereira, P. (2011) · Diabetologia · doi:10.1007/s00125-011-2191-8 · Cited by 163
HIF1α Protein Stability Is Increased by Acetylation at Lysine 709
Geng, H., Liu, Q., Xue, C., David, L. L., Beer, T. M., THOMAS, G. V., Dai, M., & Qian, D. Z. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400697 · Cited by 158
The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis
Bakleh, M. Z., & Zen, A. A. H. (2025) · Cells · doi:10.3390/cells14090673 · Cited by 190
Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing
Kabakov, A. E., & Yakimova, A. O. (2021) · Cancers · doi:10.3390/cancers13051102 · Cited by 170
Sirtuin-7 Inhibits the Activity of Hypoxia-inducible Factors
Hubbi, M. E., Hu, H., Gupta, K., Gilkes, D. M., & Semenza, G. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.476903 · Cited by 154
The Chaperone-assisted E3 Ligase C Terminus of Hsc70-interacting Protein (CHIP) Targets PTEN for Proteasomal Degradation
Ahmed, S. F., Deb, S., Paul, I., Chatterjee, A., Mandal, T., Chatterjee, U., & Ghosh, M. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.321083 · Cited by 152
Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells
Chen, S., & Sang, N. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25283 · Cited by 137
The Chaperone-Dependent Ubiquitin Ligase CHIP Targets HIF-1α for Degradation in the Presence of Methylglyoxal
Bento, C. F., Fernandes, R., Ramalho, J. S., Marques, C., Shang, F., Taylor, A., & Pereira, P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015062 · Cited by 134
Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration
Bao, L., Chen, Y., Lai, H., Wu, S.-Y., Wang, J. E., Hatanpaa, K. J., Raisanen, J. M., Fontenot, M. R., Lega, B. C., Chiang, C., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky449 · Cited by 127
Hypoxic tumor microenvironment: Implications for cancer therapy
Roy, S., Kumaravel, S., Sharma, A., Duran, C. L., Bayless, K. J., & Chakraborty, S. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220934038 · Cited by 134
Hypoxia inducible factor-1α: Its role in colorectal carcinogenesis and metastasis
Nagaraju, G. P., Bramhachari, P. V., Raghu, G., & El‐Rayes, B. F. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.06.005 · Cited by 114
A compendium of proteins that interact with HIF-1α
Semenza, G. L. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.03.041 · Cited by 118
Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases
Kim, D., Kim, K. I., & Baek, S. H. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00737-3 · Cited by 111
Cyclin-dependent kinases regulate lysosomal degradation of hypoxia-inducible factor 1α to promote cell-cycle progression
Hubbi, M. E., Gilkes, D. M., Hu, H., Gupta, K., Ahmed, I., & Semenza, G. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412840111 · Cited by 115
Protein kinase A–dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1
Bullen, J. W., Tchernyshyov, I., Holewinski, R. J., Devine, L. R., Wu, F., Venkatraman, V., KASS, D., Cole, R. N., Eyk, J. E. V., & Semenza, G. L. (2016) · Science Signaling · doi:10.1126/scisignal.aaf0583 · Cited by 107
Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury
Kim, J. Y., Barua, S., Huang, M., Park, J., Yenari, M. A., & Lee, J. E. (2020) · Cells · doi:10.3390/cells9092020 · Cited by 116
The role of HIF proteins in maintaining the metabolic health of the intervertebral disc
Silagi, E. S., Schipani, E., Shapiro, I. M., & Risbud, M. V. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00621-2 · Cited by 110
Regulation of protein turnover by heat shock proteins
Bozaykut, P., Özer, N. K., & Karademir-Yilmaz, B. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.08.012 · Cited by 105
TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition
Morin, A., Goncalves, J., Moog, S., Castro‐Vega, L. J., Job, S., Buffet, A., Fontenille, M., Woszczyk, J., Gimenez‐Roqueplo, A., Letouzé, É., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.022 · Cited by 110
Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance
Mazumder, S., Higgins, P. J., & Samarakoon, R. (2023) · Cancers · doi:10.3390/cancers15041316 · Cited by 118
TRAF6 Upregulates Expression of HIF-1α and Promotes Tumor Angiogenesis
Sun, H., Li, X., Meng, Y. J., Li, F., Li, M., & Fang, J. S. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0370 · Cited by 100
K63 linked ubiquitin chain formation is a signal for HIF1A degradation by Chaperone-Mediated Autophagy
Ferreira, J. V., Soares, A. R., Ramalho, J. S., Pereira, P., & Girão, H. (2015) · Scientific Reports · doi:10.1038/srep10210 · Cited by 107
CHIP: A Co-chaperone for Degradation by the Proteasome
Edkins, A. L. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-11731-7_11 · Cited by 96
The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth
Ban, H. S., Kim, B., Lee, H., Kim, H. M., Harmalkar, D. S., Nam, M., Park, S., Lee, K., Park, J.-T., Kim, I., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.235 · Cited by 96
Divergent expression of hypoxia response systems under deoxygenation in reef‐forming corals aligns with bleaching susceptibility
Alderdice, R., Suggett, D. J., Cárdenas, A., Hughes, D. J., Kühl, M., Pernice, M., & Voolstra, C. R. (2020) · Global Change Biology · doi:10.1111/gcb.15436 · Cited by 93
MCM Proteins Are Negative Regulators of Hypoxia-Inducible Factor 1
Hubbi, M. E., Luo, W., Baek, J. H., & Semenza, G. L. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.029 · Cited by 90
HIF-1α and HIF-2α degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc
Fujita, N., Chiba, K., Shapiro, I. M., & Risbud, M. V. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.538 · Cited by 91
Bcl-2 Regulates HIF-1α Protein Stabilization in Hypoxic Melanoma Cells via the Molecular Chaperone HSP90
Trisciuoglio, D., Gabellini, C., Desideri, M., Ziparo, E., Zupi, G., & Bufalo, D. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011772 · Cited by 95
Retracted
Extracellular glucose is crucially involved in the fate decision of LPS-stimulated RAW264.7 murine macrophage cells
Aki, T., Funakoshi, T., Noritake, K., Unuma, K., & Uemura, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-67396-6 · Cited by 89
Brusatol-Mediated Inhibition of c-Myc Increases HIF-1α Degradation and Causes Cell Death in Colorectal Cancer under Hypoxia
Oh, E., Kim, C. W., Kim, H. G., Lee, J., & Park, H. J. (2017) · Theranostics · doi:10.7150/thno.20861 · Cited by 83
Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy
Davis, L., Recktenwald, M., Hutt, E., Fuller, S., Briggs, M., Goel, A., & Daringer, N. (2022) · Cancers · doi:10.3390/cancers14051259 · Cited by 83
Vorinostat suppresses hypoxia signaling by modulating nuclear translocation of hypoxia inducible factor 1 alpha
Zhang, C., Yang, C., Feldman, M. J., Wang, H., Pang, Y., Maggio, D. M., Zhu, D., Nesvick, C. L., Dmitriev, P., Bullova, P., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18125 · Cited by 80
CHIP Promotes Human Telomerase Reverse Transcriptase Degradation and Negatively Regulates Telomerase Activity
Lee, J. H., Khadka, P., Baek, S. H., & Chung, I. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.149831 · Cited by 82
Targeting Protein–Protein Interactions in the HIF System
Wilkins, S. E., Abboud, M. I., Hancock, R. L., & Schofield, C. J. (2016) · ChemMedChem · doi:10.1002/cmdc.201600012 · Cited by 81
CHD4 Promotes Breast Cancer Progression as a Coactivator of Hypoxia-Inducible Factors
Wang, Y., Chen, Y., Bao, L., Zhang, B., Wang, J. E., Kumar, A., Xing, C., Wang, Y., & Luo, W. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1049 · Cited by 75
A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?
Joshi, V., Amanullah, A., Upadhyay, A., Mishra, R., Kumar, A., & Mishra, A. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00093 · Cited by 77
Ubiquitin ligase CHIP regulates OTUD3 stability and suppresses tumour metastasis in lung cancer
Zhang, P., Li, C., Li, H., Yuan, L., Dai, H., Peng, Z., Deng, Z., Chang, Z., Cui, C., & Zhang, L. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0571-7 · Cited by 73
Histone Deacetylase Inhibitors: The Epigenetic Therapeutics That Repress Hypoxia‐Inducible Factors
Chen, S., & Sang, N. (2010) · BioMed Research International · doi:10.1155/2011/197946 · Cited by 73
The E3 ubiquitin ligase CHIP mediates ubiquitination and proteasomal degradation of PRMT5
Zhang, H., Zeng, L., He, Q., Tao, W. A., Zha, Z., & Hu, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.001 · Cited by 70
Ubiquitin‐dependent regulation of Foxp3 and Treg function
Barbi, J. J., Pardoll, D. M., & Pan, F. (2015) · Immunological Reviews · doi:10.1111/imr.12312 · Cited by 66
HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects
Shi, Y., & Gilkes, D. M. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05537-0 · Cited by 81
Heat shock protein signaling in brain ischemia and injury
Kim, J. Y., Kim, J. W., & Yenari, M. A. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134642 · Cited by 66
HIF targets in bone remodeling and metastatic disease
Johnson, R. W., Schipani, E., & Giaccia, A. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.02.002 · Cited by 65
The endoplasmic reticulum stress and the HIF ‐1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia
López‐Hernández, B., Ceña, V., & Posadas, I. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13095 · Cited by 62
Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation
Kumar, A., Kant, S., & Singh, S. M. (2012) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2012.06.005 · Cited by 65
Regulation of hypoxia responses by flavin adenine dinucleotide‐dependent modulation of HIF‐1α protein stability
Yang, S., Park, Y. S., Cho, J. H., Moon, B., An, H., Lee, J. Y., Zhi, X., Wang, Y., Pocalyko, D. J., Lee, D. C., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201694408 · Cited by 63
Dynamic Phosphorylation of the C Terminus of Hsp70 Regulates the Mitochondrial Import of SOD2 and Redox Balance
Zemanovic, S., Ivanov, M. V., Ivanova, L. V., Bhatnagar, A., Michalkiewicz, T., Teng, R., Kumar, S. N., Rathore, R., Pritchard, K. A., Konduri, G. G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.015 · Cited by 59
The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA stability
Bett, J. S., Ibrahim, A. F. M., Garg, A. K., Kelly, V. C., Pedrioli, P. G. A., Rocha, S., & Hay, R. T. (2013) · Biochemical Journal · doi:10.1042/bj20130026 · Cited by 60
Chaperone-assisted E3 ligase CHIP: A double agent in cancer
Kumar, S., Basu, M., & Ghosh, M. K. (2021) · Genes & Diseases · doi:10.1016/j.gendis.2021.08.003 · Cited by 59
Hypoxia-Inducible Factor-1α Is Associated With Sprouting Angiogenesis in the Murine Laser-Induced Choroidal Neovascularization Model
André, H., Tunik, S., Aronsson, M., & Kvanta, A. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-16476 · Cited by 57
Ticagrelor Enhances Release of Anti-Hypoxic Cardiac Progenitor Cell-Derived Exosomes Through Increasing Cell Proliferation In Vitro
Casieri, V., Matteucci, M., Pasanisi, E. M., Papa, A., Barile, L., Fritsche‐Danielson, R., & Lionetti, V. (2020) · Scientific Reports · doi:10.1038/s41598-020-59225-7 · Cited by 57
Hypoxia-regulated gene network in drug resistance and cancer progression
Lin, S.-C., Liao, W.-L., Lee, J., & Tsai, S. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214532755 · Cited by 58
Oridonin Triggers Chaperon-mediated Proteasomal Degradation of BCR-ABL in Leukemia
Huang, H., Weng, H., Dong, B., Zhao, P., Zhou, H., & Qu, L. (2017) · Scientific Reports · doi:10.1038/srep41525 · Cited by 53
Ginsenoside Compound K Regulates HIF-1α-Mediated Glycolysis Through Bclaf1 to Inhibit the Proliferation of Human Liver Cancer Cells
Zhang, S., Zhang, M., Chen, J., Zhao, J., Su, J., & Zhang, X. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.583334 · Cited by 52
Tonicity enhancer binding protein (TonEBP) and hypoxia-inducible factor (HIF) coordinate heat shock protein 70 (Hsp70) expression in hypoxic nucleus pulposus cells: Role of Hsp70 in HIF-1α degradation
Gogate, S. S., Fujita, N., Skubutyte, R., Shapiro, I. M., & Risbud, M. V. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1571 · Cited by 51
Small molecules targeting HIF-1α pathway for cancer therapy in recent years.
Tang, W., & Zhao, G. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115235 · Cited by 50
Four-and-a-Half LIM Domain Proteins Inhibit Transactivation by Hypoxia-inducible Factor 1
Hubbi, M. E., Gilkes, D. M., Baek, J. H., & Semenza, G. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.278630 · Cited by 50
HIF-2α mediates hypoxia-induced LIF expression in human colorectal cancer cells
Wu, L., Yu, H., Zhao, Y., Zhang, C., Wang, J., Yue, X., Yang, Q., & Hu, W. (2015) · Oncotarget · doi:10.18632/oncotarget.3017 · Cited by 49
Hypoxia‐inducible factors in metabolic reprogramming during sepsis
Vanderhaeghen, T., Vandewalle, J., & Libert, C. (2020) · FEBS Journal · doi:10.1111/febs.15222 · Cited by 47
Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis
Zhan, L., Wang, W., Zhang, Y., Song, E., Fan, Y., & Wei, B. (2016) · Biochimie · doi:10.1016/j.biochi.2016.01.006 · Cited by 48
Proline-Hydroxylated Hypoxia-Inducible Factor 1α (HIF-1α) Upregulation in Human Tumours
Snell, C. E., Turley, H., McIntyre, A., Li, D., Masiero, M., Schofield, C. J., Gatter, K. C., Harris, A. L., & Pezzella, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088955 · Cited by 49
Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss
Meng, X., Lin, Z., Cao, S., Janowska, I., Sonomoto, K., Andreev, D., Knab, K., Wen, J., Knaup, K. X., Wiesener, M. S., et al. (2022) · Bone Research · doi:10.1038/s41413-022-00189-x · Cited by 50
Intermediary Metabolite Precursor Dimethyl-2-Ketoglutarate Stabilizes Hypoxia-Inducible Factor-1α by Inhibiting Prolyl-4-Hydroxylase PHD2
Hou, P., Kuo, C., Cheng, C.-T., Liou, J., Ann, D. K., & Chen, Q. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113865 · Cited by 46
Role of HSPA1L as a cellular prion protein stabilizer in tumor progression via HIF-1α/GP78 axis
Lee, J. H., Han, Y.-S., Yoon, Y. M., Yun, C. W., Yun, S. P., Kim, S. M., Kwon, H. Y., Jeong, D., Baek, M. J., Lee, H., et al. (2017) · Oncogene · doi:10.1038/onc.2017.263 · Cited by 46
A CHIPotle in physiology and disease
Paul, I., & Ghosh, M. K. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.10.027 · Cited by 45
The intricate interplay between HIFs, ROS, and the ubiquitin system in the tumor hypoxic microenvironment
Wang, Y., Liu, X., Huang, W., Liang, J., & Chen, Y. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108303 · Cited by 44
Hypoxia-induced SKA3 promoted cholangiocarcinoma progression and chemoresistance by enhancing fatty acid synthesis via the regulation of PAR-dependent HIF-1a deubiquitylation
Chen, Y., Xu, X., Wang, Y., Zhang, Y., Zhou, T., Jiang, W., Wang, Z., Chang, J., Liu, S., Chen, R., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02842-7 · Cited by 44
Role of Hypoxia and Metabolism in the Development of Neointimal Hyperplasia in Arteriovenous Fistulas
Sadaghianloo, N., Contenti, J., Dardik, A., & Mazure, N. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215387 · Cited by 45
Population Structure, and Selection Signatures Underlying High-Altitude Adaptation Inferred From Genome-Wide Copy Number Variations in Chinese Indigenous Cattle
Zhang, Y., Hu, Y., Wang, X., Jiang, Q., Zhao, H., Wang, J., Ju, Z., Yang, L., Gao, Y., Wei, X., et al. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2019.01404 · Cited by 42
Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth
Yi, X., Qi, M., Huang, M., Zhou, S., & Xiong, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.796763 · Cited by 48
Carboxyl terminus of Hsp70‐interacting protein (CHIP) contributes to human glioma oncogenesis
Xu, T., Zhou, Q., Zhou, J., Huang, Y., Yan, Y., Li, W., Wang, C., Hu, G., Lu, Y., & Chen, J. (2011) · Cancer Science · doi:10.1111/j.1349-7006.2011.01888.x · Cited by 38
The functional interplay between the HIF pathway and the ubiquitin system – more than a one-way road
Günter, J., Ruiz‐Serrano, A., Pickel, C., Wenger, R. H., & Scholz, C. C. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.03.027 · Cited by 40

Authors: Luo, W., Zhong, J., Chang, R., Hu, H., Pandey, A., & Semenza, G. L.
Affiliations: Johns Hopkins University (US)
Corresponding author: Semenza, Gregg L.
ORCID: Luo, Weibo
Zhong, Jun
Hu, Hongxia
Pandey, Akhilesh
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)
DOI: 10.1074/jbc.m109.068577
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 3891 d)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Hsp70 and CHIP Selectively Mediate Ubiquitination and Degradation of Hypoxia-inducible Factor (HIF)-1α but Not HIF-2α

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks