The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Abstract
The hypoxia-inducible factors (HIFs) 1α and 2α are key mammalian transcription factors that exhibit dramatic increases in both protein stability and intrinsic transcriptional potency during low-oxygen stress. This increased stability is due to the absence of proline hydroxylation, which in normoxia promotes binding of HIF to the von Hippel–Lindau (VHL tumor suppressor) ubiquitin ligase. We now show that hypoxic induction of the COOH-terminal transactivation domain (CAD) of HIF occurs through abrogation of hydroxylation of a conserved asparagine in the CAD. Inhibitors of Fe(II)- and 2-oxoglutarate–dependent dioxygenases prevented hydroxylation of the Asn, thus allowing the CAD to interact with the p300 transcription coactivator. Replacement of the conserved Asn by Ala resulted in constitutive p300 interaction and strong transcriptional activity. Full induction of HIF-1α and -2α, therefore, relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“It was recently shown that HIFα association with p300 is blocked under normoxic conditions by hydroxylation of a conserved asparagine residue within the CAD (Lando 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 Lando et al. 2002
In the citing paper
“As with HIF prolyl hydroxylases, endogenous HIF asparaginyl hydroxylase activity can be blocked with competitive inhibitors of 2-oxoglutarate and with iron chelators (Lando et al. 2002), suggesting that this enzyme might also resemble known hydroxylase enzymes.”
From FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor (2002) · cites this paper as Lando et al. 2002
In the citing paper
“HIF transcriptional activity is suppressed under normoxic conditions by hydroxylation of an asparagine residue within its C-terminal transactivation domain, blocking association with coactivators.”
From FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor (2002) · cites this paper as Lando et al. 2002
In the citing paper
“Full induction of the hypoxic response pathway upon exposure to low oxygen levels requires both stabilization of the HIFα transcription factor and activation of the CAD (Lando 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 Lando et al. 2002
In the citing paper
“Asparagine hydroxylation is abrogated by hypoxia, allowing HIF to recruit the larger transcriptional apparatus to hypoxiaresponsive target genes (Lando 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 Lando et al. 2002
In the citing paper
“This mechanism attenuates HIF transcriptional activity during early reoxygenation, acting as a buffer that limits the excessive metabolic activation and oxidative stress during the transition from hypoxia to normoxia”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [53]
In the citing paper
“FIH-1 functions at lower oxygen tensions than PHDs and hydroxylates a single asparagine residue within the C-terminal transactivation domain of HIF-1α, consequently limiting engagement of transcriptional co-activator complexes [52,53]”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [53]
In the citing paper
“Hif-1α is also hydroxylated in an oxygen-dependent reaction on a highly conserved asparagine residue by FIH-1 (Factor inhibiting HIF-1), which blocks the ability of Hif-1α to recruit transcriptional coactivators such as p300/CBP, in turn limiting transcriptional activation by Hif-1α under non-hypoxic conditions [45, 46].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [46]
Citations
Cites
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
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
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
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
HIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385
Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351
Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016
HIF-1 and human disease: one highly involved factor
Semenza, G. L. (2000) · Genes & Development · doi:10.1101/gad.14.16.1983 · Cited by 909
Research works printed but not linked: 1
- Supplementary material is available on Science Online at www.sciencemag.org/cgi/content/full/295/5556/858/DC1
Cited by
Sorted by citations
Items 301–400 of 1,005
Carbonic Anhydrase IX: Regulation and Role in Cancer
Benej, M., Pastoreková, S., & Pastorek, J. (2013) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-7359-2_11 · Cited by 148
The HIF pathway as a therapeutic target
Hewitson, K. S., & Schofield, C. J. (2004) · Drug Discovery Today · doi:10.1016/s1359-6446(04)03202-7 · Cited by 148
The subtle side to hypoxia inducible factor (HIFα) regulation
Bilton, R. L., & Booker, G. W. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03446.x · Cited by 150
Chen, H., Giri, N. C., Zhang, R., Yamane, K., Zhang, Y., Maroney, M. J., & Costa, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.058503 · Cited by 149
Vadlapatla, R. K., Vadlapudi, A. D., & Mitra, A. K. (2013) · Current Drug Targets · doi:10.2174/13894501113149990015 · Cited by 148
Tumor Neovascularization and Developments in Therapeutics
Katayama, Y., Uchino, J., Chihara, Y., Tamiya, N., Kaneko, Y., Yamada, T., & Takayama, K. (2019) · Cancers · doi:10.3390/cancers11030316 · Cited by 149
Ferla-Brühl, K. L., Reimann, C., JELKMANN, W. E. B., & Hellwig‐Bürgel, T. (2002) · The FASEB Journal · doi:10.1096/fj.02-0168fje · Cited by 148
Turcotte, S., Desrosiers, R. R., & Béliveau, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00427 · Cited by 147
Adenosine A 2A receptor is a unique angiogenic target of HIF-2α in pulmonary endothelial cells
Ahmad, A. M., Ahmad, S., Glover, L. E., Miller, S. M., Shannon, J. M., Guo, X., Franklin, W. A., Bridges, J. P., Schaack, J. B., Colgan, S. P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901326106 · Cited by 145
Creager, M. A., Olin, J. W., Belch, J. J. F., Moneta, G. L., Henry, T. D., Rajagopalan, S., Annex, B. H., & Hiatt, W. R. (2011) · Circulation · doi:10.1161/circulationaha.110.009407 · Cited by 146
Oncogenic Activities of IDH1/2 Mutations: From Epigenetics to Cellular Signaling
Gagné, L. M., Boulay, K., Topisirović, I., Huot, M., & Mallette, F. A. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.002 · Cited by 143
Interaction of the PAS B Domain with HSP90 Accelerates Hypoxia-Inducible Factor-1α Stabilization
Katschinski, D. M., Le, L., Schindler, S., Thomas, T., Voss, A. K., & Wenger, R. H. (2004) · Cellular Physiology and Biochemistry · doi:10.1159/000080345 · Cited by 145
Oxygen Sensing Gets a Second Wind
Bruick, R. K., & McKnight, S. L. (2002) · Science · doi:10.1126/science.1069825 · Cited by 142
Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress
Hasmim, M., Messai, Y., Ziani, L., Thiery, J., Bouhris, J.-H., Noman, M. Z., & Chouaı̈b, S. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00482 · Cited by 148
Post-translational modifications in proteins involved in blood coagulation
HANSSON, K., & Stenflo, J. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01478.x · Cited by 138
The role of hypoxia-inducible factors in cancer
Maynard, M. A., & Ohh, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7082-2 · Cited by 139
p53 and glucose metabolism: an orchestra to be directed in cancer therapy
Gomes, A. S., Ramos, H., Soares, J., & Saraiva, L. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.015 · Cited by 143
Oxygen‐dependent regulation of hypoxia‐inducible factors by prolyl and asparaginyl hydroxylation
Lando, D., Gorman, J. J., Whitelaw, M. L., & Peet, D. J. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03445.x · Cited by 138
Self-citationConditional HIF-1α Expression Produces a Reversible Cardiomyopathy
Bekeredjian, R., Walton, C. B., MacCannell, K. A., Ecker, J., Kruse, F., Outten, J. T., Sutcliffe, D. L., Gerard, R. D., Bruick, R. K., & Shohet, R. V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011693 · Cited by 138
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
Henchey, L. K., Kushal, S., Dubey, R., Chapman, R. N., Olenyuk, B. Z., & Arora, P. S. (2009) · Journal of the American Chemical Society · doi:10.1021/ja9082864 · Cited by 136
Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium
Freeman, M. F., Helf, M. J., Bhushan, A., Morinaka, B. I., & Piel, J. (2016) · Nature Chemistry · doi:10.1038/nchem.2666 · Cited by 135
The Genomics and Genetics of Oxygen Homeostasis
Semenza, G. L. (2020) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-111119-073356 · Cited by 141
Recent advances in angiogenesis, anti-angiogenesis and vascular targeting
Bikfalvi, A., & Bicknell, R. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02109-0 · Cited by 136
Hypoxia Tolerance in Animals: Biology and Application
Gorr, T. A., Wichmann, D., Hu, J., Hermes‐Lima, M., Welker, A. F., Terwilliger, N., Wren, J. F., Viney, M., Morris, S., Nilsson, G. E., et al. (2010) · Physiological and Biochemical Zoology · doi:10.1086/648581 · Cited by 134
Doege, K., Heine, S., Jensen, I., Jelkmann, W., & Metzen, E. (2005) · Blood · doi:10.1182/blood-2005-03-1138 · Cited by 128
Hypoxia and Mucosal Inflammation
Colgan, S. P., Campbell, E. L., & Kominsky, D. J. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044231 · Cited by 137
Maxwell, P. H. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000092792.97122.e0 · Cited by 134
Regulation of Vascular Endothelial Growth Factor Synthesis by Nitric Oxide: Facts and Controversies
Dulak, J., & Józkowicz, A. (2003) · Antioxidants & Redox Signaling · doi:10.1089/152308603321223612 · Cited by 130
Mitochondrial regulation of oxygen sensing
Bell, E. L., Emerling, B. M., & Chandel, N. S. (2005) · Mitochondrion · doi:10.1016/j.mito.2005.06.005 · Cited by 130
Battaglia, V., Compagnone, A., Bandino, A., Bragadin, M., Rossi, C. A., Zanetti, F., Colombatto, S., GRILLO, M. A., & Toninello, A. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.07.012 · Cited by 132
Carrot and stick: HIF-α engages c-Myc in hypoxic adaptation
Huang, E. L. (2008) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402302 · Cited by 133
Koivunen, P., Hirsilä, M., Kivirikko, K. I., & Myllyharju, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604628200 · Cited by 129
Favier, F. B., Britto, F. A., Freyssenet, D. G., Bigard, X. A., & Benoit, H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2025-9 · Cited by 135
Flashman, E., Davies, S. L., Yeoh, K. K., & Schofield, C. J. (2010) · Biochemical Journal · doi:10.1042/bj20091609 · Cited by 133
Barteczek, P., Li, L., Ernst, A., Böhler, L.-I., Marti, H. H., & Kunze, R. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15624933 · Cited by 132
Su, H., Arakawa-Hoyt, J. S., & Kan, Y. W. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132275299 · Cited by 129
Persistent induction of HIF‐1α and ‐2α in cardiomyocytes and stromal cells of ischemic myocardium
Jürgensen, J. S., Rosenberger, C., Wiesener, M. S., Warnecke, C., Hörstrup, J. H., Gräfe, M., Philipp, S., Griethe, W., Maxwell, P. H., Frei, U. A., et al. (2004) · The FASEB Journal · doi:10.1096/fj.04-1605fje · Cited by 131
Pharmacological targeting of the HIF hydroxylases – A new field in medicine development
Chan, M. C., Holt‐Martyn, J. P., Schofield, C. J., & Ratcliffe, P. J. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.01.001 · Cited by 128
Fan, J., He, Q., Liu, Y., Zhang, F., Yang, X., Wang, Z., Lu, N., Fan, W., Lin, L., Niu, G., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b03737 · Cited by 127
HIF-1 in Cell Cycle Regulation, Apoptosis, and Tumor Progression
Goda, N., Dozier, S. J., & Johnson, R. S. (2003) · Antioxidants and Redox Signaling · doi:10.1089/152308603768295212 · Cited by 132
Induction of ID2 Expression by Hypoxia-inducible Factor-1
Löfstedt, T., Jögi, A., Sigvardsson, M., Gradin, K., Poellinger, L., Påhlman, S., & Axelson, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402904200 · Cited by 126
Godschalk, R., van Schooten, F., & Bartsch, H. (2003) · BMB Reports · doi:10.5483/bmbrep.2003.36.1.001 · Cited by 131
Recombinant protein expression: Challenges in production and folding related matters
Beygmoradi, A., Homaei, A. A., Hemmati, R., & Fernandes, P. C. D. B. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.123407 · Cited by 133
Role of hypoxia-inducible factor-1α as a cancer therapy target
Patiar, S., & Harris, A. L. (2006) · Endocrine Related Cancer · doi:10.1677/erc.1.01290 · Cited by 124
Hypoxia. Hypoxia in the pathogenesis of systemic sclerosis
Beyer, C., Schett, G. A., Gay, S., Distler, O., & Distler, J. H. W. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2598 · Cited by 131
The role of oxygen in ruminant preimplantation embryo development and metabolism
Harvey, A. J. (2006) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2006.10.008 · Cited by 123
Osada, M., Imaoka, S., & Funae, Y. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.08.036 · Cited by 124
Structure–function relationships of human JmjC oxygenases—demethylases versus hydroxylases
Markolovic, S., Leissing, T. M., Chowdhury, R., Wilkins, S. E., Lü, X., & Schofield, C. J. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.05.013 · Cited by 125
von Hippel-Lindau Tumor Suppressor Protein and Hypoxia-Inducible Factor in Kidney Cancer
Maynard, M. A., & Ohh, M. (2003) · American Journal of Nephrology · doi:10.1159/000075346 · Cited by 126
Oxygen sensing and oxidant/redox-related pathways
Haddad, J. J. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.02.162 · Cited by 123
Michalak, K. P., & Michalak, A. Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1558263 · Cited by 148
Brain Protection by Erythropoietin: A Manifold Task
Rabie, T., & Marti, H. H. (2008) · Physiology · doi:10.1152/physiol.00016.2008 · Cited by 123
Induction of T-type Calcium Channel Gene Expression by Chronic Hypoxia
Toro, R. D., Levitsky, K. L., López‐Barneo, J., & Chiara, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212576200 · Cited by 118
Lee, C., Kim, S. J., Jeong, D. G., Lee, S. M., & Ryu, S. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210385200 · Cited by 124
Makino, Y., Uenishi, R., Okamoto, K., Isoe, T., Hosono, O., Tanaka, H., Kanopka, A., Poellinger, L., Haneda, M., & Morimoto, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700732200 · Cited by 120
Prolyl 4‐hydroxylases, master regulators of the hypoxia response
Myllyharju, J. (2013) · Acta Physiologica · doi:10.1111/apha.12096 · Cited by 123
Development of novel therapeutic strategies that target HIF-1
Semenza, G. L. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.2.267 · Cited by 120
Chen, S., Yin, C., Lao, T., Liang, D., He, D., Wang, C., & Sang, N. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1055426 · Cited by 127
Eltzschig, H. K., MacManus, C. F., & Colgan, S. P. (2008) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2008.01.006 · Cited by 121
Pasanen, A., Heikkilä, M. M., Rautavuoma, K., Hirsilä, M., Kivirikko, K. I., & Myllyharju, J. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.04.008 · Cited by 126
Hypoxia, drug therapy and toxicity
Lee, K., Roth, R. A., & LaPres, J. J. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.08.001 · Cited by 118
Hypoxia-induced angiogenesis in human hepatocellular carcinoma
Kim, K.-R., Moon, H.-E., & Kim, K. (2002) · Journal of Molecular Medicine · doi:10.1007/s00109-002-0380-0 · Cited by 117
NO restores HIF-1α hydroxylation during hypoxia: Role of reactive oxygen species
Callapina, M., Zhou, J., Schmid, T., Köhl, R., & Brüne, B. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.05.009 · Cited by 118
Janssen, H. L., Haustermans, K. M., Sprong, D., Blommestijn, G. J. F., Hofland, I., Hoebers, F. J. P., Blijweert, E., Raleigh, J. A., Semenza, G. L., Varia, M. A., et al. (2002) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(02)03935-4 · Cited by 116
Zou, D., Zhang, Z., He, J., Zhu, S., Wang, S., Zhang, W., Zhou, J., Xu, Y., Huang, Y., Wang, Y., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.09.005 · Cited by 115
A Nontranscriptional Role for HIF-1α as a Direct Inhibitor of DNA Replication
Hubbi, M. E., Kshitiz, Gilkes, D. M., Rey, S., Wong, C. C., Luo, W., Kim, D.-H., Dang, C. V., Levchenko, A., & Semenza, G. L. (2013) · Science Signaling · doi:10.1126/scisignal.2003417 · Cited by 116
HIFs, Hypoxia, and Vascular Development
Covello, K. L., & Simon, M. C. (2004) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)62002-3 · Cited by 117
Role of the Glucocorticoid Receptor for Regulation of Hypoxia-dependent Gene Expression
Kodama, T., Shimizu, N., Yoshikawa, N., Makino, Y., Ouchida, R., Okamoto, K., Hisada, T., Nakamura, H., Morimoto, C., & Tanaka, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302581200 · Cited by 116
McNeill, L. A., Flashman, E., Buck, M. R., Hewitson, K. S., Clifton, I. J., Jeschke, G., Claridge, T. D. W., Ehrismann, D., Oldham, N. J., & Schofield, C. J. (2005) · Molecular BioSystems · doi:10.1039/b511249b · Cited by 113
A dynamic model of the hypoxia-inducible factor 1-alpha (HIF-1α) network
Nguyen, L. K., Cavadas, M. A. S., Scholz, C. C., Fitzpatrick, S. F., Brüning, U., Cummins, E. P., Tambuwala, M. M., Manresa, M. C., Kholodenko, B. Ν., Taylor, C. T., et al. (2013) · Journal of Cell Science · doi:10.1242/jcs.119974 · Cited by 115
Hoppe, G., Yoon, S., Gopalan, B., Savage, A. R., Brown, R. D., Case, K. R., Vasanji, A., Chan, E. R., Silver, R. B., & Sears, J. E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523005113 · Cited by 118
Bidirectional modulation of HIF-2 activity through chemical ligands
Wu, D., Su, X., Lu, J.-P., Li, S., Hood, B. L., Vasile, S., Potluri, N., Diao, X., Kim, Y., Khorasanizadeh, S., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0234-5 · Cited by 116
Hypoxia-inducible factor-1 in tumour angiogenesis
Shi, Y., & Fang, W. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i8.1082 · Cited by 117
Ye, S., Riplinger, C., Hansen, A., Krebs, C., Bollinger, J. M., Jr., & Neese, F. (2012) · Chemistry - A European Journal · doi:10.1002/chem.201102829 · Cited by 114
Hypoxia-inducible factor as a therapeutic target for cardioprotection
Ong, S., & Hausenloy, D. J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.005 · Cited by 113
Graham, A. M., & Presnell, J. S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179545 · Cited by 117
The hypoxia-adenosine link during inflammation
Bowser, J. L., Lee, J. W., Yuan, X., & Eltzschig, H. K. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00101.2017 · Cited by 118
mRNA-to-protein translation in hypoxia
Chee, N. T., Lohse, I., & Brothers, S. P. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0968-4 · Cited by 115
Tumor Dormancy and Interplay with Hypoxic Tumor Microenvironment
Butturini, E., de Prati, A. C., Boriero, D., & Mariotto, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174305 · Cited by 123
Distler, J. H. W., Wenger, R. H., Gassmann, M., Kurowska, W., Astrid, H., Gay, S., & Distler, O. (2004) · Arthritis & Rheumatism · doi:10.1002/art.11425 · Cited by 112
Sirtuin 7 in cell proliferation, stress and disease: Rise of the Seventh Sirtuin!
Kiran, S., Anwar, T., Kiran, M., & Ramakrishna, G. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.11.026 · Cited by 113
Functional Analysis of Hypoxia-inducible Factor-1α-mediated Transactivation
Ruas, J. L., Poellinger, L., & Pereira, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205051200 · Cited by 116
Genetic regulation of cell function in response to iron overload or chelation
Templeton, D. M., & Liu, Y. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00497-x · Cited by 112
The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases
Acker, T., Fandrey, J., & Acker, H. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.04.008 · Cited by 112
EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination
Gómez-Maldonado, L., Tiana, M., Roche, O., Prado‐Cabrero, A., Jensen, L. D., Fernández‐Barral, A., Guijarro-Muñoz, I., Favaro, E., Moreno‐Bueno, G., Sanz, L., et al. (2014) · Oncogene · doi:10.1038/onc.2014.200 · Cited by 113
Chan, M. C., Ilott, N. E., Schödel, J., Sims, D., Tumber, A., Lippl, K., Mole, D. R., Pugh, C. W., Ratcliffe, P. J., Ponting, C. P., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.749291 · Cited by 113
HIF-α Prolyl Hydroxylase Inhibitors and Their Implications for Biomedicine: A Comprehensive Review
Hirota, K. (2021) · Biomedicines · doi:10.3390/biomedicines9050468 · Cited by 115
Malignant Glioma Physiology: Cellular Response to Hypoxia and Its Role in Tumor Progression
Brat, D. J., & Mapstone, T. B. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-138-8-200304150-00014 · Cited by 113
PCAF is an HIF-1α cofactor that regulates p53 transcriptional activity in hypoxia
Xenaki, G., Ontikatze, T., Rajendran, R., Stratford, I. J., Dive, C., Krstic–Demonacos, M., & Demonacos, C. (2008) · Oncogene · doi:10.1038/onc.2008.192 · Cited by 112
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
The role of hypoxia and acidosis in promoting metastasis and resistance to chemotherapy
DeClerck, K. (2009) · Frontiers in bioscience · doi:10.2741/3616 · Cited by 113
Antioxidant enzymes and redox regulating thiol proteins in malignancies of human lung
Kinnula, V. L., Pääkkö, P. K., & Soini, Y. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.05.045 · Cited by 110
Impaired Oxygen-dependent Reduction of HIF-1α and -2α Proteins in Pre-eclamptic Placentae
Rajakumar, A., Doty, K. D., Daftary, A., Harger, G. F., & Conrad, K. P. (2003) · Placenta · doi:10.1053/plac.2002.0893 · Cited by 108
Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-κB Activation
An, J., Mo, D., Liu, H., Veena, M. S., Srivatsan, E. S., Massoumi, R., & Rettig, M. B. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.10.007 · Cited by 115
The human oxygen sensing machinery and its manipulation
Chowdhury, R., Hardy, A., & Schofield, C. J. (2008) · Chemical Society Reviews · doi:10.1039/b701676j · Cited by 115
Haddad, J. J. (2002) · Respiratory Research · doi:10.1186/rr190 · Cited by 110
Interaction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2
Guzman, R. N. D., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310348200 · Cited by 109
Fath, D. M., Kong, X., Liang, D., Lin, Z., Chou, A. D., Jiang, Y., Fang, J., Caro, J., & Sang, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600456200 · Cited by 108
Kaluz, S., Kaluzová, M., & Stanbridge, E. J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00552-06 · Cited by 108
Metadata
- Authors
- Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L.
- Affiliations
- Adelaide University (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Corresponding author
- Whitelaw, Murray L.
- Venue
- Science
- Published
- 2002-02
- Volume
- 295
- Issue
- 5556
- Pages
- 858-861
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1973092951
- Semantic Scholar
- 56986a3761858ed94221534104f97dacadfc3a98
- Cited by
- 1,558
- References
- 28
- Citations by year
- 2026: 25 · 2025: 31 · 2024: 34 · 2023: 46 · 2022: 46 · 2021: 48 · 2020: 43 · 2019: 50 · 2018: 50 · 2017: 48 · 2016: 58 · 2015: 58 · 2014: 58 · 2013: 67 · 2012: 58
- FWCI
- 49.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- hypoxia-inducible factor, HIF-1α, HIF-2α, proline hydroxylation, transactivation domain, p300 coactivator, protein stability, 2-oxoglutarate-dependent dioxygenase, transcriptional activation, hypoxia
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Amino Acid Sequence, Animals, Asparagine, Cell Line, Humans, Mixed Function Oxygenases, Hydroxylation, Molecular Sequence Data, Mutation, Oxygen, Proline, Recombinant Fusion Proteins, Mass Spectrometry, Transcription Factors, Transcriptional Activation, Trans-Activators, Cell Hypoxia, Protein Structure, Tertiary, Amino Acid Substitution, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit
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
