The VHL tumor suppressor: master regulator of HIF

Haase, Volker

doi:10.2174/138161209789649394

Cited by 175Cancer, Hypoxia, and MetabolismEar and Head TumorsErythropoietin and Anemia Treatment

The VHL tumor suppressor: master regulator of HIF

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Haase, Volker·2009·Current Pharmaceutical Design

DOI 10.2174/138161209789649394PMC PMC3622710

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Abstract

Hypoxia-Inducible Factors (HIFs) are heterodimeric oxygen-sensitive basic helix-loop-helix transcription factors that play central roles in cellular adaptation to low oxygen environments. The von-Hippel Lindau tumor suppressor (pVHL) is the substrate recognition component of an E3 ubiquitin ligase and functions as a master regulator of HIF activity by targeting the hydroxylated HIF-alpha subunit for ubiquitylation and rapid proteasomal degradation under normoxic conditions. Mutations in pVHL can be found in familial and sporadic hemangioblastomas, clear cell carcinomas of the kidney, pheochromocytomas and inherited forms of erythrocytosis, illustrating the importance of disrupted molecular oxygen sensing in the pathogenesis of these diseases. Tissue-specific gene targeting of pVHL in mice has demonstrated that efficient execution of HIF proteolysis is critically important for normal tissue physiology, and has provided novel insights into the functional consequences of HIF activation on the cellular and tissue level. Here we focus on the contribution of individual HIF transcription factors to the development of VHL phenotypes and discuss how the pVHL/HIF axis could be exploited pharmacologically.

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HIFs can be activated independently of hypoxia by oncogene activation or tumor suppressor loss.
“Independently of hypoxia, HIFs can also become activated through the activation of oncogenes, or loss of tumor suppressor genes.”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [13]
The “pVHL: MASTER REGULATOR OF HIF” section (page unavailable) says that mutated pVHL or loss of VHL expression increases HIF activity irrespective of oxygen levels. The paper does not establish the other proposed route—oncogene activation causing HIF activation. Its discussion of c-Myc concerns interaction with HIF, not that causal claim. (LLM, conf=0.88)
Experimental — accuracy not yet measured
RAS, PI-3K, ERK1/2 activation and pVHL loss cause hypoxia-independent HIF activation.
“Similarly, activation of RAS, PI-3K, or downstream ERK1/2 kinases, common in many cancer types, and loss of pVHL, frequently observed in clear cell renal cell carcinoma (ccRCC), result in hypoxia-independent activation of the HIFs [12–14].”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [13]
The “pVHL: MASTER REGULATOR OF HIF” section states that loss of VHL expression stabilizes HIF-α and increases HIF activity irrespective of oxygen levels. The passages found do not support the additional claim that activation of RAS, PI-3K, or ERK1/2 causes hypoxia-independent HIF activation. (LLM, conf=0.87)
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Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · see citing works
Mutations of the VHL tumour suppressor gene in renal carcinoma
Gnarra, J. R., Tory, K., Weng, Y., Schmidt, L., Wei, M. H., Li, H., Latif, F., Liu, S., Chen, F., Duh, F.-M., et al. (1994) · Nature Genetics · doi:10.1038/ng0594-85 · Cited by 1,730 · see citing works
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 · see citing works
von Hippel-Lindau disease
Lonser, R. R., Glenn, G. M., Walther, M. M., Chew, E. Y., Libutti, S. K., Linehan, W. M., & Oldfield, E. H. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13643-4 · Cited by 1,615 · see citing works
Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel–Lindau protein
Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577 · see citing works
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558 · see citing works
FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · cited 1× · see citing works
“Inhibition of FIH under hypoxic conditions facilitates CBP/p300 recruitment, resulting in increased HIF target gene expression in VHL-deficient cell lines or under pronounced hypoxia [42–45].”
Background
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386 · see citing works
FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene
Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., & Comoglio, P. M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00085-0 · Cited by 1,311 · see citing works
Hypoxia requires Notch signaling to maintain the undifferentiated cell state
Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U., & Bondesson, M. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.010 · Cited by 1,109 · see citing works
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.
Ravi, R. K., Mookerjee, B., Bhujwalla, Z. M., Sutter, T. R., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · PubMed Central · Cited by 1,099 · see citing works
Hypoxia Inducible Factor-α Binding and Ubiquitylation by the von Hippel-Lindau Tumor Suppressor Protein
Cockman, M. E., Masson, N., Mole, D. R., Jaakkola, P., Chang, G.-W., Clifford, S. C., Maher, E. R., Pugh, C. W., Ratcliffe, P. J., & Maxwell, P. H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002740200 · Cited by 1,053 · see citing works
Integration of Oxygen Signaling at the Consensus HRE
Wenger, R. H., Stiehl, D. P., & Camenisch, G. (2005) · Science's STKE · doi:10.1126/stke.3062005re12 · Cited by 1,032 · see citing works
Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · see citing works
Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma
Raval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940 · see citing works
Role of VHL Gene Mutation in Human Cancer
Kim, W. Y., & Kaelin, W. G. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.061 · Cited by 940 · see citing works
Mechanism of regulation of the hypoxia‐inducible factor‐1α by the von Hippel‐Lindau tumor suppressor protein
Tanimoto, K., Makino, Y., Pereira, T., & Poellinger, L. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4298 · Cited by 928 · see citing works
Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL
Staller, P., Sulitkova, J., Lisztwan, J., Moch, H., Oakeley, E. J., & Krek, W. (2003) · Nature · doi:10.1038/nature01874 · Cited by 870 · see citing works
Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function
Stebbins, C. E., Kaelin, W. G., & Pavletich, N. P. (1999) · Science · doi:10.1126/science.284.5413.455 · Cited by 852 · see citing works
Stabilization of wild-type p53 by hypoxia-inducible factor 1α
An, W. G., Kanekal, M., Simon, M. C., Maltepe, E., Blagosklonny, M. V., & Neckers, L. Μ. (1998) · Nature · doi:10.1038/32925 · Cited by 820 · see citing works
HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796 · see citing works
Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase
Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin, W. G., Elledge, S. J., Conaway, R. C., et al. (1999) · Science · doi:10.1126/science.284.5414.657 · Cited by 786 · see citing works
HIF-2α Promotes Hypoxic Cell Proliferation by Enhancing c-Myc Transcriptional Activity
Gordan, J. D., Bertout, J. A., Hu, C.-J., Diehl, J. A., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.006 · Cited by 781 · see citing works
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., & Kaelin, W. G. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00043-0 · Cited by 761 · see citing works
Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL
Hon, W.-C., Wilson, M. I., Harlos, K., Claridge, T. D. W., Schofield, C. J., Pugh, C. W., Maxwell, P. H., Ratcliffe, P. J., Stuart, D. I., & Jones, E. Y. (2002) · Nature · doi:10.1038/nature00767 · Cited by 751 · see citing works
Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression
Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., & Poellinger, L. (2001) · Nature · doi:10.1038/35107085 · Cited by 705 · see citing works
Binding of the von Hippel-Lindau Tumor Suppressor Protein to Elongin B and C
Kibel, A. S., Iliopoulos, O., DeCaprio, J. A., & Kaelin, W. G. (1995) · Science · doi:10.1126/science.7660130 · Cited by 664 · see citing works
HIF-1α induces cell cycle arrest by functionally counteracting Myc
Koshiji, M., Kageyama, Y., Pete, E. A., Horikawa, I., Barrett, J. C., & Huang, L. E. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600196 · Cited by 652 · see citing works
Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex
Kamura, T., Sato, S., Iwaï, K., Czyzyk-Krzeska, M., Conaway, R. C., & Conaway, J. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190332597 · Cited by 652 · see citing works
Inhibition of HIF2α Is Sufficient to Suppress pVHL-Defective Tumor Growth
Kondo, K., Kim, W. Y., Lechpammer, M., & Kaelin, W. G. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000083 · Cited by 611 · see citing works
Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer
Thomas, G. V., Tran, C., Mellinghoff, I. K., Welsbie, D. S., Chan, E., Fueger, B., Czernin, J., & Sawyers, C. L. (2006) · Nature Medicine · doi:10.1038/nm1337 · Cited by 604 · see citing works
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596 · see citing works
Self-citation
Expression of Hypoxia-Inducible Factor-1α and -2α in Hypoxic and Ischemic Rat Kidneys
Rosenberger, C., Mandriota, S. J., Jürgensen, J. S., Wiesener, M. S., Hörstrup, J. H., Frei, U. A., Ratcliffe, P. J., Maxwell, P. H., Bachmann, S., & Eckardt, K. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000017223.49823.2a · Cited by 566 · see citing works
Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor
Ivan, M., Haberberger, T., Gervasi, D. C., Michelson, K. S., Günzler, V., Kondo, K., Yang, H., Sorokina, I., Conaway, R. C., Conaway, J. W., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192342099 · Cited by 561 · see citing works
Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia
Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., et al. (2002) · Nature Genetics · doi:10.1038/ng1019 · Cited by 510 · see citing works
Identification of the von Hippel–Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex
Iwai, K., Yamanaka, K., Kamura, T., Minato, N., Conaway, R. C., Conaway, J. W., Klausner, R. D., & Pause, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12436 · Cited by 508 · see citing works
HIF-α effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma
Gordan, J. D., Lal, P., Dondeti, V. R., Letrero, R., Parekh, K. N., Oquendo, C. E., Greenberg, R. A., Flaherty, K. T., Rathmell, W. K., Keith, B., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.10.016 · Cited by 493 · see citing works
The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins
Pause, A., Lee, S., Worrell, R., Chen, D. Y. T., Burgess, W. H., Linehan, W. M., & Klausner, R. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2156 · Cited by 492 · see citing works
HIF activation identifies early lesions in VHL kidneys
Mandriota, S. J., Turner, K. J., Davies, D. R., Murray, P. G., Morgan, N. V., Sowter, H. M., Wykoff, C. C., Maher, E. R., Harris, A. L., Ratcliffe, P. J., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00071-5 · Cited by 483 · see citing works
The von Hippel-Lindau Tumor Suppressor Protein Is Required for Proper Assembly of an Extracellular Fibronectin Matrix
Ohh, M., Yauch, R. L., Lonergan, K. M., Whaley, J. M., Stemmer-Rachamimov, A. O., Louis, D. N., Gavin, B. J., Kley, N., Kaelin, W. G., & Iliopoulos, O. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80096-9 · Cited by 472 · see citing works
Acute postnatal ablation of Hif-2 α results in anemia
Gruber, M., Hu, C.-J., Johnson, R. S., Brown, E. J., Keith, B., & Simon, M. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608382104 · Cited by 457 · see citing works
Silencing of Epidermal Growth Factor Receptor Suppresses Hypoxia-Inducible Factor-2–Driven VHL −/− Renal Cancer
Smith, K., Gunaratnam, L., Morley, M., Franovic, A., Mekhail, K., & Lee, S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0169 · Cited by 456 · see citing works
The contribution of VHL substrate binding and HIF1-α to the phenotype of VHL loss in renal cell carcinoma
Maranchie, J. K., Vasselli, J. R., Riss, J., Bonifacino, J. S., Linehan, W. M., & Klausner, R. D. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00044-2 · Cited by 433 · see citing works
Vascular tumors in livers with targeted inactivation of the von Hippel–Lindau tumor suppressor
Haase, V. H., Glickman, J. N., Socolovsky, M., & Jaenisch, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1583 · Cited by 421 · see citing works
Self-citation
Hypoxia-Inducible Factor-1-Dependent Repression of E-cadherin in von Hippel-Lindau Tumor Suppressor–Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B
Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J. H., & Semenza, G. L. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3719 · Cited by 415 · see citing works
Placental but Not Heart Defects Are Associated with Elevated Hypoxia-Inducible Factor α Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2
Takeda, K., Ho, V. C., Takeda, H., Duan, L.-J., Nagy, A., & Fong, G.-H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00425-06 · Cited by 401 · see citing works
Differentiating the functional role of hypoxia‐inducible factor (HIF)‐1α and HIF‐2α (EPAS‐1) by the use of RNA interference: erythropoietin is a HIF‐2α target gene in Hep3B and Kelly cells
Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V. A., Frei, U. A., Wiesener, M. S., & Eckardt, K. (2004) · The FASEB Journal · doi:10.1096/fj.04-1640fje · Cited by 395 · see citing works
von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF.
Hoffman, M. A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.10.1019 · Cited by 382 · see citing works
The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activityPreprint
Lisztwan, J. H., Imbert, G., Wirbelauer, C., Gstaiger, M., & Krek, W. (1999) · Genes & Development · doi:10.1101/gad.13.14.1822 · Cited by 380 · see citing works
Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease
Clifford, S. C. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.10.1029 · Cited by 373 · see citing works
Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
Gnarra, J. R., Ward, J. M., Porter, F. D., WAGNER, J. R., Devor, D. E., Grinberg, A., Emmert‐Buck, M. R., Westphal, H., Klausner, R. D., & Linehan, W. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9102 · Cited by 362 · see citing works
Renal Cyst Development in Mice with Conditional Inactivation of the von Hippel-Lindau Tumor Suppressor
Rankin, E. B., Tomaszewski, J. E., & Haase, V. H. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3241 · Cited by 356 · see citing works
Self-citation
Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL
Hergovich, A., Lisztwan, J. H., Barry, R. E., Ballschmieter, P., & Krek, W. (2002) · Nature Cell Biology · doi:10.1038/ncb899 · Cited by 334 · see citing works
Preconditional Activation of Hypoxia-Inducible Factors Ameliorates Ischemic Acute Renal Failure
Bernhardt, W. M., Accent]mpean, V. C. C., Kany, S., Diaeresis]rgensen, J.-S. J., Weidemann, A., Warnecke, C., Arend, M., Klaus, S. J., Diaeresis]nzler, V. G., Amann, K., et al. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005121302 · Cited by 294 · see citing works
Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease
Yoder, B. K. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006111215 · Cited by 288 · see citing works
Multiple Splice Variants of the Human HIF-3α Locus Are Targets of the von Hippel-Lindau E3 Ubiquitin Ligase Complex
Maynard, M. A., Qi, H., Chung, J., Lee, E. H. L., Kondo, Y., Hara, S., Conaway, R. C., Conaway, J. W., & Ohh, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208681200 · Cited by 283 · see citing works
Role of hypoxia-inducible factor in cell survival during myocardial ischemia–reperfusion
Loor, G., & Schumacker, P. T. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.13 · Cited by 276 · see citing works
Differential Regulation of the Transcriptional Activities of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) and HIF-2α in Stem Cells
Hu, C., Iyer, S. R., Sataur, A., Covello, K. L., Chodosh, L. A., & Simon, M. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3514-3526.2006 · Cited by 267 · see citing works
Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation.
TURNER, K. J., Moore, J. W., Jones, A., Taylor, C., Cuthbert-Heavens, D., Cheng, H., Leek, R., Gatter, K. C., Maxwell, P. H., Ratcliffe, P. J., et al. (2002) · PubMed · Cited by 264 · see citing works
Regulation of E-cadherin Expression by VHL and Hypoxia-Inducible Factor
Esteban, M. A., Tran, M. G. B., Harten, S. K., Hill, P., Castellanos, M. C., Chandra, A., Raval, R., O'Brien, T. S., & Maxwell, P. H. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2670 · Cited by 262 · see citing works
VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail
Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00892-06 · Cited by 248 · see citing works
Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL−/− tumors
Zimmer, M., Doucette, D., Siddiqui, N., & Iliopoulos, O. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.89.2.2 · Cited by 244 · see citing works
p53 Stabilization and Transactivation by a von Hippel-Lindau Protein
Roe, J., Kim, H., Lee, S.-M., Kim, S.-T., Cho, E., & Youn, H. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.04.006 · Cited by 240 · see citing works
Formation of the VHL–Elongin BC Tumor Suppressor Complex Is Mediated by the Chaperonin TRiC
Feldman, D. E., Thulasiraman, V., Ferreyra, R. G., & Frydman, J. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80233-6 · Cited by 238 · see citing works
pVHL and GSK3β are components of a primary cilium-maintenance signalling network
Thoma, C. R., Frew, I. J., Hoerner, C. R., Montani, M., Moch, H., & Krek, W. (2007) · Nature Cell Biology · doi:10.1038/ncb1579 · Cited by 238 · see citing works
Failure to prolyl hydroxylate hypoxia‐inducible factor α phenocopies VHL inactivation in vivo
Kim, W. Y., Safran, M., Buckley, M. R., Ebert, B. L., Glickman, J., Bosenberg, M., Regan, M., & Kaelin, W. G. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601300 · Cited by 235 · see citing works
von Hippel–Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination
Kuznetsova, A. V., Meller, J., Schnell, P. O., Nash, J. A., Ignacak, M. L., Sánchez, Y., Conaway, J. W., Conaway, R. C., & Czyzyk-Krzeska, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436037100 · Cited by 230 · see citing works
The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells
Koochekpour, S., Jeffers, M., Wang, P. H., Gong, C., Taylor, G. A., Roessler, L. M., Stearman, R. S., Vasselli, J. R., Stetler‐Stevenson, W. G., Kaelin, W. G., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.5902 · Cited by 201 · see citing works
Regulation of endocytosis via the oxygen-sensing pathway
Wang, Y., Roche, O., Yan, M. S., Finak, G., Evans, A. J., Metcalf, J. L., Hast, B. E., Hanna, S. C., Wondergem, B., Furge, K. A., et al. (2009) · Nature Medicine · doi:10.1038/nm.1922 · Cited by 193 · see citing works
von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease
Vortmeyer, A. O., Gnarra, J. R., Emmert-Buck, M. R., Katz, D., Linehan, W. M., Oldfield, E. H., & Zhuang, Z. (1997) · Human Pathology · doi:10.1016/s0046-8177(97)90075-7 · Cited by 189 · see citing works
Jade-1 inhibits Wnt signalling by ubiquitylating β-catenin and mediates Wnt pathway inhibition by pVHL
Chitalia, V. C., Foy, R. L., Bachschmid, M. M., Zeng, L., Panchenko, M. V., Zhou, M. I., Bharti, A., Seldin, D. C., Lecker, S. H., Dominguez, I., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1781 · Cited by 182 · see citing works
pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2
Yang, H., Minamishima, Y. A., Yan, Q., Schlisio, S., Ebert, B. L., Zhang, X., Zhang, L., Kim, W. Y., Olumi, A. F., & Kaelin, W. G. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.09.010 · Cited by 179 · see citing works
Targeted Inactivation of Fh1 Causes Proliferative Renal Cyst Development and Activation of the Hypoxia Pathway
Pollard, P. J., Spencer‐Dene, B., Shukla, D., Howarth, K. M., Nye, E. L., El-Bahrawy, M. A., Deheragoda, M. G., Kolatsi‐Joannou, M., McDonald, S. A. C., Martin, A., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.005 · Cited by 177 · see citing works
The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C
Okuda, H., Saitoh, K., Hirai, S.-I., Iwaï, K., Takaki, Y., Baba, M., Minato, N., Ohno, S., & Shuin, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107880200 · Cited by 176 · see citing works
The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth
Schermer, B., Ghenoiu, C., Bartram, M. P., Müller, R., Kotsis, F., Höhne, M., Kühn, W., Rapka, M., Nitschke, R., Zentgraf, H., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200605092 · Cited by 172 · see citing works
HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques
Hsieh, M. M., Linde, N. S., Wynter, A., Metzger, M., Wong, C., Langsetmo, I., Lin, A., Smith, R., Rodgers, G. P., Donahue, R. E., et al. (2007) · Blood · doi:10.1182/blood-2007-02-073254 · Cited by 171 · see citing works
Activation of Sp1-mediated Vascular Permeability Factor/Vascular Endothelial Growth Factor Transcription Requires Specific Interaction with Protein Kinase C ζ
Pal, S., Claffey, K. P., Cohen, H. T., & Mukhopadhyay, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.41.26277 · Cited by 162 · see citing works
Formation of Primary Cilia in the Renal Epithelium Is Regulated by the von Hippel-Lindau Tumor Suppressor Protein
Esteban, M. A., Harten, S. K., Tran, M. G. B., & Maxwell, P. H. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006020181 · Cited by 160 · see citing works
pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation
Frew, I. J., Thoma, C. R., Georgiev, S., Minola, A., Hitz, M., Montani, M., Moch, H., & Krek, W. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.96 · Cited by 156 · see citing works
Ubiquitination of a Novel Deubiquitinating Enzyme Requires Direct Binding to von Hippel-Lindau Tumor Suppressor Protein
Li, Z., Na, X., Wang, D., Schoen, S. R., Messing, E. M., & Wu, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108269200 · Cited by 155 · see citing works
Genetic Analysis of the Role of the Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-inducible Factor (HIF) in Regulating HIF Transcriptional Target Genes
Stolze, I. P., Tian, Y.-M., Appelhoff, R. J., Turley, H., Wykoff, C. C., Gleadle, J., & Ratcliffe, P. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406713200 · Cited by 155 · see citing works
Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease
Zatyka, M., da Silva, N. F., Clifford, S. C., Morris, M. R., Wiesener, M. S., Eckardt, K., Houlston, R. S., Richards, F. M., Latif, F., & Maher, E. R. (2002) · PubMed · doi:10.25405/ncl.34582002 · Cited by 147 · see citing works
Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice
Rankin, E. B., Rha, J., Unger, T. L., Wu, C., Shutt, H. P., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2008) · Oncogene · doi:10.1038/onc.2008.160 · Cited by 145 · see citing works
Self-citation
Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans
Bishop, T., Lau, K. W., Epstein, A. C. R., Kim, S. K., Jiang, M., O’Rourke, D., Pugh, C. W., Gleadle, J., Taylor, M. S., Hodgkin, J., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020289 · Cited by 145 · see citing works
The von Hippel-Lindau Gene Product Inhibits Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Renal Cell Carcinoma by Blocking Protein Kinase C Pathways
Pal, S., Claffey, K. P., Dvorak, H. F., & Mukhopadhyay, D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.27509 · Cited by 143 · see citing works
Primary Cilium Formation Requires von Hippel-Lindau Gene Function in Renal-Derived Cells
Lutz, M. S., & Burk, R. D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0501 · Cited by 137 · see citing works
Inactivation of the Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Suppresses von Hippel-Lindau Disease-Associated Vascular Tumors in Mice
Rankin, E. B., Higgins, D. F., Walisser, J. A., Johnson, R. S., Bradfield, C. A., & Haase, V. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.8.3163-3172.2005 · Cited by 137 · see citing works
Self-citation
Deletion ofVhlhin chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development
Pfander, D., Kobayashi, T., Knight, M. C., Zelzer, E., Chan, D. A., Olsen, B. R., Giaccia, A. J., Johnson, R. S., Haase, V. H., & Schipani, E. (2004) · Development · doi:10.1242/dev.01138 · Cited by 128 · see citing works
Self-citation
VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.
Bindra, R. S., Vasselli, J. R., Stearman, R. S., Linehan, W. M., & Klausner, R. D. (2002) · PubMed · Cited by 127 · see citing works
Characterization of a von Hippel Lindau Pathway Involved in Extracellular Matrix Remodeling, Cell Invasion, and Angiogenesis
Kurban, G., Hudon, V., Duplan, E., Ohh, M., & Pause, A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2560 · Cited by 126 · see citing works
Up-Regulation of Vascular Endothelial Growth Factor in Stromal Cells of Hemangioblastomas Is Correlated with Up-Regulation of the Transcription Factor HRF/HIF-2α
Flamme, I., Krieg, M., & Plate, K. H. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65541-1 · Cited by 119 · see citing works
Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene.
Ma, W., Tessarollo, L., Hong, S., Baba, M., Southon, E. A., Back, T. C., Spence, S. E., Lobe, C. G., Sharma, N. D., Maher, G., et al. (2003) · PubMed · Cited by 112 · see citing works
Renal cysts, renal cancer and von Hippel-Lindau disease
Neumann, H. P. H., & Zbar, B. (1997) · Kidney International · doi:10.1038/ki.1997.3 · Cited by 112 · see citing works
von Hippel–Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2α signaling and splenic erythropoiesis
Hickey, M. M., Lam, J. C., Bezman, N. A., Rathmell, W. K., & Simon, M. C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32614 · Cited by 110 · see citing works
Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes
Biju, M. P., Neumann, A. K., Bensinger, S. J., Johnson, R. S., Turka, L. A., & Haase, V. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9038-9047.2004 · Cited by 110 · see citing works
Self-citation
VHL Induces Renal Cell Differentiation and Growth Arrest through Integration of Cell-Cell and Cell-Extracellular Matrix Signaling
Davidowitz, E. J., Schoenfeld, A. R., & Burk, R. D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.865-874.2001 · Cited by 105 · see citing works
Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene
Wykoff, C. C., Sotiriou, C. P., Cockman, M. E., Ratcliffe, P. J., Maxwell, P. H., Liu, E., & Harris, A. L. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601657 · Cited by 99 · see citing works
The von Hippel–Lindau tumor suppressor gene product represses oncogenic β-catenin signaling in renal carcinoma cells
Peruzzi, B., Athauda, G., & Bottaro, D. P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606850103 · Cited by 95 · see citing works
Dominant-Negative HIF-3α4 Suppresses VHL-Null Renal Cell Carcinoma Progression
Maynard, M. A., Evans, A. J., Shi, W., Kim, W. Y., Liu, F., & Ohh, M. (2007) · Cell Cycle · doi:10.4161/cc.6.22.4947 · Cited by 92 · see citing works
Collagen matrix assembly is driven by the interaction of von Hippel–Lindau tumor suppressor protein with hydroxylated collagen IV alpha 2
Kurban, G., Duplan, E., Ramlal, N., Hudon, V., Sado, Y., Ninomiya, Y., & Pause, A. (2007) · Oncogene · doi:10.1038/sj.onc.1210709 · Cited by 91 · see citing works
Genotype–phenotype correlations in von hippel–lindau disease
Neumann, H. P. H., & Bender, B. (1998) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1998.00336.x · Cited by 89 · see citing works
Inhibition of Insulin-like Growth Factor-I-mediated Cell Signaling by the von Hippel-Lindau Gene Product in Renal Cancer
Datta, K., Nambudripad, R., Pal, S., Zhou, M., Cohen, H. T., & Mukhopadhyay, D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909970199 · Cited by 84 · see citing works
The von Hippel-Lindau Tumor Suppressor Stabilizes Novel Plant Homeodomain Protein Jade-1
Zhou, M. I., Wang, H., Ross, J. J., Kuzmin, I., Xu, C., & Cohen, H. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205040200 · Cited by 80 · see citing works
The 104-123 amino acid sequence of the beta-domain of von Hippel-Lindau gene product is sufficient to inhibit renal tumor growth and invasion.
Datta, K., Sundberg, C. J., Karumanchi, S. A., & Mukhopadhyay, D. (2001) · PubMed · Cited by 78 · see citing works
The VHL protein recruits a novel KRAB‐A domain protein to repress HIF‐1α transcriptional activity
Li, Z., Wang, D., Na, X., Schoen, S. R., Messing, E. M., & Wu, G. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg173 · Cited by 77 · see citing works
von Hippel-Lindau Tumor Suppressor Protein Regulates the Assembly of Intercellular Junctions in Renal Cancer Cells through Hypoxia-Inducible Factor–Independent Mechanisms
Calzada, M. J., Esteban, M. A., Feijoo‐Cuaresma, M., Castellanos, M. C., Naranjo‐Suarez, S., Temes, E., Méndez, F., Yáñez‐Mó, M., Ohh, M., & Landázuri, M. O. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3236 · Cited by 74 · see citing works
Untitled work
(2005) · PubMed · Cited by 72 · see citing works
Tumor Suppressor von Hippel-Lindau (VHL) Stabilization of Jade-1 Protein Occurs through Plant Homeodomains and Is VHL Mutation Dependent
Zhou, M. I., Wang, H., Foy, R. L., Ross, J. J., & Cohen, H. T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0884 · Cited by 64 · see citing works
The Von Hippel-Lindau Protein Interacts with Heteronuclear Ribonucleoprotein A2 and Regulates Its Expression
Pioli, P. A., & Rigby, W. F. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105391200 · Cited by 63 · see citing works
Case report: Multiple hepatic and pulmonary haemangioblastomas — A new manifestation of von Hippel-Lindau disease
McGrath, F. P., Gibney, R. G., Morris, D. C., Owen, D. A., & Erb, S. (1992) · Clinical Radiology · doi:10.1016/s0009-9260(05)81467-9 · Cited by 51 · see citing works
Hepatic hemangioblastoma. An unusual presentation in a patient with von Hippel-Lindau disease.
Rojiani, A. M., Owen, D. A., Berry, K., Woodhurst, B., Anderson, F., Scudamore, C. H., & Erb, S. (1991) · PubMed · Cited by 48 · see citing works
Combined Vhlh and Pten Mutation Causes Genital Tract Cystadenoma and Squamous Metaplasia
Frew, I. J., Minola, A., Georgiev, S., Hitz, M., Moch, H., Richard, S., Vortmeyer, A. O., & Krek, W. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02132-07 · Cited by 43 · see citing works

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Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
Jonasch, E., Donskov, F., Iliopoulos, O., Rathmell, W. K., Narayan, V. K., Maughan, B. L., Oudard, S., Else, T., Maranchie, J. K., Welsh, S. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103425 · Cited by 714 · see citing works
“Urinary tract infection 7 (11) 1 (2) 5 (8) 1 (2)”
CD8+ T cell metabolism in infection and cancer
Reina‐Campos, M., Scharping, N. E., & Goldrath, A. W. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00537-8 · Cited by 630 · see citing works
Clinical update on cancer: molecular oncology of head and neck cancer
Suh, Y., Amelio, I., Urbano, T. G., & Tavassoli, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2013.548 · Cited by 190 · see citing works
The Impact of Hypoxia in Early Pregnancy on Placental Cells
Zhao, H. F., Wong, R. J., & Stevenson, D. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189675 · Cited by 183 · see citing works
Biomarkers Predicting Outcome in Patients with Advanced Renal Cell Carcinoma: Results from Sorafenib Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial
Peña, C. E., Lathia, C. D., Shan, M., Escudier, B. J., & Bukowski, R. M. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3343 · Cited by 173 · see citing works
Novel anemia therapies in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Ku, E., Vecchio, L. D., Eckardt, K., Haase, V. H., Johansen, K. L., Nangaku, M., Tangri, N., Waikar, S. S., Więcek, A., Cheung, M., et al. (2023) · Kidney International · doi:10.1016/j.kint.2023.05.009 · Cited by 156 · see citing works
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Hypoxia and the phenomenon of immune exclusion
Pietrobon, V., & Marincola, F. M. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-020-02667-4 · Cited by 119 · see citing works
P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection
Jenster, L., Lange, K.-E., Normann, S., Hemdt, A. V., Wuerth, J. D., Schiffelers, L. D. J., Tesfamariam, Y. M., Gohr, F. N., Klein, L., Kaltheuner, I. H., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220837 · Cited by 113 · see citing works
STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection
Gomes, M. T. R., Guimarães, E. S., Marinho, F. V., Macedo, I., Aguiar, E. R. G. R., Barber, G. N., Moraes‐Vieira, P. M., Alves-Filho, J. C., & Oliveira, S. C. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009597 · Cited by 116 · see citing works
Genomics and epigenomics of clear cell renal cell carcinoma: Recent developments and potential applications
Rydzanicz, M., Wrzesiński, T., Bluyssen, H. A. R., & Wesoły, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.08.006 · Cited by 112 · see citing works
Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells
Jeong, J., Gurunathan, S., Kang, M.-H., Han, J. W., Das, J., Choi, Y., Kwon, D., Cho, S., Park, C., Seo, H. G., et al. (2016) · Scientific Reports · doi:10.1038/srep21688 · Cited by 106 · see citing works
Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury
Jablonska, B., Gierdalski, M., Chew, L., Hawley, T. S., Catron, M. A., Lichauco, A. M., Cabrera‐Luque, J., Yuen, T. J., Rowitch, D. H., & Gallo, V. (2016) · Nature Communications · doi:10.1038/ncomms13866 · Cited by 94 · see citing works
CHIP/Stub1 functions as a tumor suppressor and represses NF- B-mediated signaling in colorectal cancer
Wang, Y., Ren, F., Wang, Y., Feng, Y., Wang, D., Jia, B., Qiu, Y., Wang, S., Yu, J. Q., Sung, J. J. �., et al. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt393 · Cited by 91 · see citing works
Novel insights into the polycythemia–paraganglioma–somatostatinoma syndrome
Därr, R., Nambuba, J., Rivero, J. D., Janssen, I., Merino, M. J., Todorović, M., Balint, B., Jochmanová, I., Prchal, J. T., Lechan, R. M., et al. (2016) · Endocrine Related Cancer · doi:10.1530/erc-16-0231 · Cited by 84 · see citing works
The Synergistic Cooperation between TGF-β and Hypoxia in Cancer and Fibrosis
Mallikarjuna, P., Zhou, Y., & Landström, M. (2022) · Biomolecules · doi:10.3390/biom12050635 · Cited by 82 · see citing works
Identification of Cys255 in HIF‐1α as a novel site for development of covalent inhibitors of HIF‐1α/ARNT PasB domain protein–protein interaction
Cardoso, R., Love, R., Nilsson, C. L., Bergqvist, S., Nowlin, D., Yan, J., Liu, K. K. ‐., Zhu, J., Chen, P., Deng, Y., et al. (2012) · Protein Science · doi:10.1002/pro.2172 · Cited by 79 · see citing works
Low tumor glutathione level as a sensitivity marker for glutamate‑cysteine ligase inhibitors
Nishizawa, S., Araki, H., Ishikawa, Y., Kitazawa, S., Hata, A., Soga, T., & Hara, T. (2018) · Oncology Letters · doi:10.3892/ol.2018.8447 · Cited by 70 · see citing works
The Correlation of Expression Levels of HIF-1 and HIF-2 in Hepatocellular Carcinoma with Capsular Invasion, Portal Vein Tumor Thrombi and Patients' Clinical Outcome
Yang, S., Liu, L.-P., Jiang, J., Xiong, Z., He, Q.-J., & Wu, C. (2013) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyt194 · Cited by 69 · see citing works
TET2 Suppresses VHL Deficiency-Driven Clear Cell Renal Cell Carcinoma by Inhibiting HIF Signaling
Zhang, X., Li, S., He, J., Jin, Y., Zhang, R., Dong, W., Lin, M., Yang, Y., Tian, T., Zhou, Y., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-3013 · Cited by 65 · see citing works
Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma
Yu, C., Yang, S., Fang, X., JIANG, J.-X., Sun, C., & Huang, T. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3199 · Cited by 58 · see citing works
Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression
Lukitasari, M., Nugroho, D. A., & Widodo, N. (2018) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x18789628 · Cited by 57 · see citing works
Non-canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function
Allan, K. C., Hu, L. R., Scavuzzo, M. A., Morton, A. R., Gevorgyan, A. S., Cohn, E. F., Clayton, B. L. L., Bederman, I. R., Hung, S., Bartels, C. F., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.09.019 · Cited by 62 · see citing works
The HILDA Complex Coordinates a Conditional Switch in the 3′-Untranslated Region of the VEGFA mRNA
Yao, P., Potdar, A. A., Ray, P. S., Eswarappa, S. M., Flagg, A. C., Willard, B. B., & Fox, P. L. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001635 · Cited by 56 · see citing works
Long Noncoding RNAs and Stress Response in the Nucleolus
Пирогов, С. А., Gvozdev, V. A., & Klenov, M. S. (2019) · Cells · doi:10.3390/cells8070668 · Cited by 54 · see citing works
Adaptations to a hypoxic lifestyle in naked mole-rats
Pamenter, M. E. (2022) · Journal of Experimental Biology · doi:10.1242/jeb.196725 · Cited by 53 · see citing works
Changing Paradigms in the Treatment of Malignant Pheochromocytoma
Grogan, R. H., Mitmaker, E. J., & Duh, Q. (2011) · Cancer Control · doi:10.1177/107327481101800205 · Cited by 54 · see citing works
Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy
Veliça, P., Cunha, P. P., Vojnovic, N., Foskolou, I. P., Bargiela, D., Gojkovic, M., Rundqvist, H., & Johnson, R. S. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0561 · Cited by 52 · see citing works
“In the presence of oxygen, HIF-α subunits are 19 hydroxylated at two conserved prolines by prolyl-hydroxylases (PHD), leading to 20 recognition and ubiquitination by the Von Hippel-Lindau (VHL) protein and resulting in 21 proteasomal degradation (13,14).”
Background
Epo and Non-hematopoietic Cells: What Do We Know?
Ogunshola, O. O., & Bogdanova, A. Y. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-308-4_2 · Cited by 51 · see citing works
Belzutifan for von Hippel-Lindau disease-associated renal cell carcinoma and other neoplasms (LITESPARK-004): 50 months follow-up from a single-arm, phase 2 study
Srinivasan, R., Iliopoulos, O., Beckermann, K. E., Narayan, V., Maughan, B. L., Oudard, S., Else, T., Maranchie, J. K., Iversen, A. B., Cornell, J., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(25)00099-3 · Cited by 50 · see citing works
Inhibition of breast cancer stem-like cells by a triterpenoid, ursolic acid, via activation of Wnt antagonist, sFRP4 and suppression of miRNA-499a-5p
Mandal, S., Gamit, N., Varier, L., Dharmarajan, A., & Warrier, S. R. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118854 · Cited by 49 · see citing works
Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease
Dias, F., Teixeira, A. L., Nogueira, I., Morais, M., Maia, J., Bodo, C., Ferreira, M., Silva, A., Vilhena, M., Lobo, J., et al. (2020) · Cancers · doi:10.3390/cancers12061450 · Cited by 48 · see citing works
Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer
Pal, K., Madamsetty, V. S., Dutta, S. K., Wang, E., Angom, R. S., & Mukhopadhyay, D. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0105-2 · Cited by 46 · see citing works
Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges
Ye, P., Chi, X., Cha, J., Luo, S., Yang, G., Yan, X., & Yang, W. (2021) · Cells · doi:10.3390/cells10123309 · Cited by 49 · see citing works
Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease
Curran, C. S., & Kopp, J. B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.782199 · Cited by 46 · see citing works
UK kidney association clinical practice guideline: update of anaemia of chronic kidney disease
Bhandari, S., Spencer, S., Oliveira, B., Mikhail, A. I., Brooks, O., Bryant, G., Willicombe, M. K., Baines, R. J., Alldridge, L. C., & Haslam-England, S. (2025) · BMC Nephrology · doi:10.1186/s12882-025-04115-1 · Cited by 46 · see citing works
Current Status and Future Directions of Immunotherapy in Renal Cell Carcinoma
Considine, B., & Hurwitz, M. E. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0779-1 · Cited by 47 · see citing works
Increased HIF-1α Expression Correlates With Cell Proliferation and Vascular Markers CD31 and VEGF-A in Uveal Melanoma
Mouriaux, F., Sanschagrin, F., Diorio, C., Landreville, S., Comoz, F., Petit, E., Bernaudin, M., Rousseau, A. P., Bergeron, D., & Morcos, M. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13345 · Cited by 48 · see citing works
The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation
Acuña-Pilarte, K., & Koh, M. Y. (2025) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2025.06.005 · Cited by 41 · see citing works
Gerometabolites: The pseudohypoxic aging side of cancer oncometabolites
Menéndez, J. A., Alarcón, T., & Joven, J. (2014) · Cell Cycle · doi:10.4161/cc.28079 · Cited by 41 · see citing works
MicroRNAs and altered metabolism of clear cell renal cell carcinoma: Potential role as aerobic glycolysis biomarkers
Morais, M., Dias, F., Teixeira, A. L., & Medeiros, R. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.05.028 · Cited by 41 · see citing works
CK2 and the Hallmarks of Cancer
Firnau, M.-B., & Brieger, A. (2022) · Biomedicines · doi:10.3390/biomedicines10081987 · Cited by 41 · see citing works
Engineering Next-Generation CAR-T Cells: Overcoming Tumor Hypoxia and Metabolism
Gao, T. A., & Chen, Y. Y. (2022) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-092120-092914 · Cited by 41 · see citing works
Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma
Sainero‐Alcolado, L., Garde-Lapido, E., Snaebjornsson, M. T., Schoch, S., Stevens, I., Ruiz-Pérez, M. V., Dyrager, C., Pelechano, V., Axelson, H., Schulze, A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2310479121 · Cited by 36 · see citing works
Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets
Gore, M., Kabekkodu, S. P., & Chakrabarty, S. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189292 · Cited by 39 · see citing works
IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia
Kuo, Y., Au, H., Hsu, J., Wang, H.-F., Lee, C.-J., Peng, S.-W., Lai, S.-C., Wu, Y.-C., Ho, H., & Huang, Y. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.12.003 · Cited by 36 · see citing works
Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study
Else, T., Jonasch, E. W., Iliopoulos, O., Beckermann, K. E., Narayan, V., Maughan, B. L., Oudard, S. M., Maranchie, J. K., Iversen, A. B. B., Goldberg, C. M., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2592 · Cited by 33 · see citing works
Theranostic application of miR-429 in HER2+ breast cancer
Cava, C., Novello, C., Martelli, C., Dico, A. L., Ottobrini, L., Piccotti, F., Truffi, M., Corsi, F., Bertoli, G. R., & Castiglioni, I. (2019) · Theranostics · doi:10.7150/thno.36274 · Cited by 33 · see citing works
Frontiers in PROTACs
Hughes, G. R., Dudey, A. P., Hemmings, A. M., & Chantry, A. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.04.010 · Cited by 33 · see citing works
Melatonin and Prostate Cancer: Anti-tumor Roles and Therapeutic Application
Megerian, M. F., Kim, J., Badreddine, J., Hong, S. H., Ponsky, L. E., Shin, J. I., & Ghayda, R. A. (2022) · Aging and Disease · doi:10.14336/ad.2022.1010 · Cited by 30 · see citing works
The molecular mechanism of NF-κB dysregulation across different subtypes of renal cell carcinoma
Jayab, N. N. A., Abed, A., Talaat, I. M., & Hamoudi, R. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.07.030 · Cited by 31 · see citing works
IFN-γ and CD38 in Hyperprogressive Cancer Development
Angelicola, S., Ruzzi, F., Landuzzi, L., Scalambra, L., Gelsomino, F., Ardizzoni, A., Nanni, P., Lollini, P., & Palladini, A. (2021) · Cancers · doi:10.3390/cancers13020309 · Cited by 29 · see citing works
Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors
Choi, W. W., Boland, J. L., Kalola, A., & Lin, J. (2023) · Current Oncology Reports · doi:10.1007/s11912-022-01354-5 · Cited by 29 · see citing works
Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α)
Zhao, G., Liu, Y., Fang, J., Chen, Y., Li, H., & Gao, K. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.062 · Cited by 27 · see citing works
Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis
Tomc, J., & Debeljak, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137074 · Cited by 27 · see citing works
MDM2-Driven Ubiquitination Rapidly Removes p53 from Its Cognate Promoters
Henningsen, K. M., Manzini, V., Magerhans, A., Gerber, S., & Dobbelstein, M. (2021) · Biomolecules · doi:10.3390/biom12010022 · Cited by 27 · see citing works
Nek1 phosphorylates Von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization
Patil, M., Pabla, N., Huang, S., & Dong, Z. (2012) · Cell Cycle · doi:10.4161/cc.23053 · Cited by 25 · see citing works
Activation of Hypoxia Signaling in Stromal Progenitors Impairs Kidney Development
Broeker, K. A. E., Steppan, D., Fuchs, M., Wagner, C., Willam, C., Kurtz, A., & Kurt, B. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.03.014 · Cited by 25 · see citing works
Neurological applications of belzutifan in von Hippel-Lindau disease
Zhang, Y., Nguyen, C. C., Zhang, N., Fink, N. S., John, J. D., Venkatesh, O., Roe, J., Hoffman, S. C., Lesniak, M. S., Wolinsky, J., et al. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac234 · Cited by 24 · see citing works
The hypoxia-inducible factor 1 pathway plays a critical role in the development of breast muscle myopathies in broiler chickens: a comprehensive review
Alnahhas, N., Pouliot, É., & Saucier, L. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1260987 · Cited by 25 · see citing works
Long non-coding RNA GEHT1 promoted the proliferation of ovarian cancer cells via modulating the protein stability of HIF1α
Liu, D., & Li, H. (2019) · Bioscience Reports · doi:10.1042/bsr20181650 · Cited by 23 · see citing works
Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer
Shih, H.-J., Chang, H., Chen, C., & Torng, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-02400-1 · Cited by 23 · see citing works
Polyphyllin I ameliorates gefitinib resistance and inhibits the VEGF/VEGFR2/p38 pathway by targeting HIF-1a in lung adenocarcinoma
Zhang, D., Tian, X., Wang, Y., Liu, F., Zhang, J., Wang, H., Zhang, N., Yan, T., Lin, C., Shi, Z., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155690 · Cited by 23 · see citing works
Role of Hypoxia-Inducible Factors in Acute Kidney Injury
Andringa, K. K., & Agarwal, A. (2014) · Nephron Clinical Practice · doi:10.1159/000363669 · Cited by 22 · see citing works
Tivozanib for the treatment of renal cell carcinoma
Santoni, M., Massari, F., Piva, F., Carrozza, F., Nunno, V. D., Cimadamore, A., Martignetti, A., Montironi, R., & Battelli, N. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1480722 · Cited by 22 · see citing works
Inhibition of Hypoxia-Inducible Transcription Factor (HIF-1α) Signaling with Sulfonyl-γ-AApeptide Helices
Jiang, W., Abdulkadir, S., Zhao, X., Sang, P., Τοματσίδου, Α., Zhang, X., Chen, Y., Calcul, L., Sun, X., Cheng, F., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c06694 · Cited by 22 · see citing works
Systematically characterizing the roles of E3-ligase family members in inflammatory responses with massively parallel Perturb-seqPreprint
Geiger-Schuller, K., Eraslan, B., Kuksenko, O., Dey, K. K., Jagadeesh, K. A., Thakore, P. I., Karayel, Ö., Yung, A. R., Rajagopalan, A. R., Meireles, A. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.23.525198 · Cited by 21 · see citing works
Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis
Tacelli, M., Gentiluomo, M., Biamonte, P., Castano, J. P., Berković, M. C., Cives, M., Kapitanović, S., Marinoni, I., Marinović, S., Nikas, I. P., et al. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.03.005 · Cited by 21 · see citing works
The link between obesity and aging - insights into cardiac energy metabolism
Owesny, P., & Grune, T. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111870 · Cited by 21 · see citing works
CD105 in the progression and therapy of renal cell carcinoma
Oladejo, M., Nguyen, H.-M., & Wood, L. M. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216327 · Cited by 20 · see citing works
The Janus face of HIF-1α in ischemic stroke and the possible associated pathways
Amin, N., Abbasi, I. N., Wu, F., Shi, Z., Sundus, J., Badry, A., Yuan, X., Zhao, B., Pan, J., Mi, X., et al. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105747 · Cited by 20 · see citing works
Targeting the prostate tumor microenvironment by plant-derived natural products
Wu, J., Ji, H., Li, T., Guo, H., Xu, H., Zhu, J., Tian, J., Gao, M., Wang, X., & Zhang, A. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.111011 · Cited by 19 · see citing works
Using a yeast two-hybrid system to identify FTCD as a new regulator for HIF-1α in HepG2 cells
Yu, Z., Ge, Y., Xie, L., Zhang, T., Huang, L., Zhao, X., Liu, J., & Huang, G. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.03.016 · Cited by 19 · see citing works
Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities
Awan, A. B., Osman, M. J. A., & Khan, O. M. (2025) · Cells · doi:10.3390/cells14020069 · Cited by 18 · see citing works
Metabolic Alterations at the Crossroad of Aging and Oncogenesis
Raffaghello, L., & Longo, V. D. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.01.003 · Cited by 18 · see citing works
Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma
Xiao-fen, W., Ting, C., Li, J., Deng-yang, M., Zhu, Q., & Xin, L. (2016) · Open Medicine · doi:10.1515/med-2016-0043 · Cited by 17 · see citing works
Von Hippel-Lindau syndrome: clinical features, genetic foundations, and management strategies
Harbi, E., & Aschner, M. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10403-8 · Cited by 16 · see citing works
Pathogenicity of VHL variants in families with non-syndromic von Hippel-Lindau phenotypes: An integrated evaluation of germline and somatic genomic results
Rana, H. Q., Koeller, D. R., Schwartz, A., Manning, D. K., Schneider, K. A., Krajewski, K. M., Choueiri, T. K., Lindeman, N. I., Garber, J. E., & Ghazani, A. A. (2021) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2021.104359 · Cited by 16 · see citing works
TCF3 regulates human endometrial stromal cell proliferation and migration in RPL
Wei, X., Liu, X.-Q., Zhang, Y.-C., Qin, C.-M., Lin, Y., & Tian, F.-J. (2022) · Reproduction · doi:10.1530/rep-21-0463 · Cited by 16 · see citing works
Expression and significance of HIF-1α and HIF-2α in pancreatic cancer
Wang, M., Chen, M.-Y., Guo, X., & Jiang, J. (2015) · Journal of Huazhong University of Science and Technology [Medical Sciences] · doi:10.1007/s11596-015-1521-3 · Cited by 16 · see citing works
Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery
McDermott, A., & Tavassoli, A. (2024) · Transcription · doi:10.1080/21541264.2024.2417475 · Cited by 15 · see citing works
The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma?
Cinque, A., Minnei, R., Floris, M., & Trevisani, F. (2022) · Cancers · doi:10.3390/cancers14215352 · Cited by 15 · see citing works
Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma
Pośpiech, E., Ligęza, J., Wilk, W., Gołas, A., Jaszczyński, J., Stelmach, A., Ryś, J., Blecharczyk, A., Wojas‐Pelc, A., Jura, J., et al. (2015) · BioMed Research International · doi:10.1155/2015/860405 · Cited by 15 · see citing works
Role of Biomarkers in Prediction of Response to Therapeutics in Metastatic Renal-Cell Carcinoma
Adashek, J. J., Salgia, M. M., Posadas, E. M., Figlin, R. A., & Gong, J. (2019) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2019.01.004 · Cited by 15 · see citing works
Integrative Models of Histopathological Image Features and Omics Data Predict Survival in Head and Neck Squamous Cell Carcinoma
Zeng, H., Chen, L., Huang, Y., Luo, Y., & Ma, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.553099 · Cited by 15 · see citing works
Lactate Influences the Gene Expression Profile of Human Mesenchymal Stem Cells (hMSC) in a Dose Dependant Manner
Schneider, C. C., Ateschrang, A., Königsrainer, I., Glatzle, J., Bühler, S., Schäfer, R., Northoff, H., Königsrainer, A., & Zieker, D. (2012) · Cellular Physiology and Biochemistry · doi:10.1159/000343342 · Cited by 15 · see citing works
The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience
Zamarud, A., Marianayagam, N. J., Park, D. J., Yener, U., Yoo, K. H., Meola, A., & Chang, S. D. (2023) · Journal of Neuro-Oncology · doi:10.1007/s11060-023-04496-z · Cited by 14 · see citing works
Sulforaphane blocks hypoxia-mediated resistance to TRAIL-induced tumor cell death
Park (2011) · Molecular Medicine Reports · doi:10.3892/mmr.2011.422 · Cited by 14 · see citing works
TCEB2 confers resistance to VEGF-targeted therapy in ovarian cancer
Deng, Z., Zhou, J., Han, X., & Li, X. (2015) · Oncology Reports · doi:10.3892/or.2015.4388 · Cited by 14 · see citing works
Inhibition of autophagy enhanced cobalt chloride‑induced apoptosis in rat alveolar type�II epithelial cells
Yu, Y., Li, W., Ren, L., Yang, C., Li, D., Han, X., Sun, Y., Lv, C., & Han, F. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9209 · Cited by 14 · see citing works
MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression
Talwar, H. S., Bouhamdan, M., Bauerfeld, C. P., Talreja, J., Aoidi, R., Houde, N., Charron, J., & Samavati, L. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801477 · Cited by 14 · see citing works
Effects of hypoxia‐inducible factor‐1α and hypoxia‐inducible factor‐2α overexpression on hepatocellular carcinoma survival: A systematic review with meta‐analysis
Ding, Z., Dong, Z., Chen, Z., Yang, Y., Yan, L., Li, H., Liu, K., Yao, C., Yan, Y., Yang, C., et al. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15395 · Cited by 12 · see citing works
The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain
Stegen, M., & Frey, U. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415880 · Cited by 12 · see citing works
The Protective Role of pVHL in Imiquimod-Induced Psoriasis-like Skin Inflammation
Martínez-Torres, I., Tepale-Segura, A., Castro-Escamilla, O., Cancino‐Díaz, J. C., Rodríguez–Martínez, S., Pérez‐Tapia, S. M., Bonifaz, L. C., & Cancino-Diaz, M. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095226 · Cited by 11 · see citing works
Target therapy in metastatic pheochromocytoma: current perspectives and controversies
Mohammed, A. A., Elshentenawy, A., Sherisher, M. A., & EL-Khatib, H. M. (2014) · Oncology Reviews · doi:10.4081/oncol.2014.249 · Cited by 11 · see citing works
Expression of hypoxia-inducible factor 3α in hepatocellular carcinoma and its association with other hypoxia-inducible factors
LIU, P., Fang, X., Song, Y., JIANG, J.-X., He, Q., & Liu, X.-Z. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3193 · Cited by 11 · see citing works
743 Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function
Scharping, N. E., Ge, X., Matias, M. I., Jiang, F., Cafferata, A., Heeg, M., Monell, A., Galletti, G., Cheung, K. P., Rock, A. E., et al. (2025) · Cell · doi:10.1016/j.cell.2026.02.019 · Cited by 12 · see citing works
Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy
Youssef, E. M., Zhao, S., Purcell, C., Olson, G. L., & El‐Deiry, W. S. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1484515 · Cited by 10 · see citing works
EDDM3A drives gastric cancer progression by promoting HIF-1α-dependent aerobic glycolysis
Wu, T., Yang, Y., Zhang, B., Zhang, Z.-S., Zhou, S. F., Jia, G., Liu, S., He, X., He, J.-X., & Wang, N. (2022) · Oncogenesis · doi:10.1038/s41389-022-00379-6 · Cited by 10 · see citing works
The human testis-enriched HSPA2 interacts with HIF-1α in epidermal keratinocytes, yet HIF-1α stability and HIF-1-dependent gene expression rely on the HSPA (HSP70) activity
Sojka, D. R., Gogler‐Pigłowska, A., Kania, D., Vydra, N., Wiecha, K., Adamiec‐Organiściok, M., Wilk, A., Chumak, V., Matysniak, D. P., & Ścieglińska, D. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119735 · Cited by 9 · see citing works
Molecularly Enriched Pathways and Differentially Expressed Genes Distinguishing Cutaneous Squamous Cell Carcinoma From Pseudoepitheliomatous Hyperplasia
Seong, H., Su, A., Li, X., & Binder, S. W. (2013) · Diagnostic Molecular Pathology · doi:10.1097/pdm.0b013e3182707894 · Cited by 9 · see citing works

The VHL tumor suppressor and HIF: insights from genetic studies in mice
Kapitsinou, P. P., & Haase, V. H. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402313 · Cited by 151 · see citing works
Self-citation
The von Hippel–Lindau tumor suppressor protein: new insights into oxygen sensing and cancer
Kim, W., & Kaelin, W. G. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00010-2 · Cited by 174 · see citing works
Transcriptional Regulation of Genes via Hypoxia-Inducible Factor
Roche, O., & Ohh, M. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-376-9_13 · Cited by 14 · see citing works
The von Hippel–Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis
Pugh, C. W., & Ratcliffe, P. J. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00103-7 · Cited by 202 · see citing works
The von Hippel-Lindau Tumor Suppressor Protein: Roles in Cancer and Oxygen SensingPreprint
Kaelin, W. G. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.001 · Cited by 69 · see citing works

Authors: Haase, V.
Affiliations: Vanderbilt University Medical Center (US)
Corresponding author: Haase, Volker
ORCID: Haase, Volker
Venue: Current Pharmaceutical Design
Publisher: Bentham Science Publishers Ltd.
Published: 2009-11-01
Volume: 15
Issue: 33
Pages: 3895-3903
ISSN: 1381-6128 (ISSN-L)
DOI: 10.2174/138161209789649394
PMC: PMC3622710
OpenAlex: W2067955850
Cited by: 175
References: 114
Citations by year: 2026: 5 · 2025: 27 · 2024: 19 · 2023: 21 · 2022: 20 · 2021: 18 · 2020: 10 · 2019: 9 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 5 · 2014: 8 · 2013: 6 · 2012: 5
FWCI: 1.01
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Current Pharmaceutical Design (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA100787)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080821, R01DK081646)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Oncology › Ear and Head Tumors
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Keywords: von Hippel-Lindau tumor suppressor, hypoxia-inducible factor, ubiquitin ligase, proteasomal degradation, oxygen sensing, hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma, erythrocytosis, HIF-targeted therapy
MeSH terms: Animals, Humans, Mutation, Phenotype, Drug Delivery Systems, Gene Targeting, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Ubiquitination

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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 ›

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The VHL tumor suppressor: master regulator of HIF

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