The von Hippel–Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis

On the Origin of Cancer Cells

1956 • 12,141 citations

Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

1995 • 5,971 citations

Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O ₂ -Regulated Prolyl Hydroxylation

2001 • 5,255 citations

The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis

1999 • 4,973 citations

HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O ₂ Sensing

2001 • 4,537 citations

Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1

1996 • 3,851 citations

C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation

2001 • 3,215 citations

Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene

1993 • 2,906 citations

Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects

2001 • 2,558 citations

A Conserved Family of Prolyl-4-Hydroxylases That Modify HIF

2001 • 2,481 citations

Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis

1998 • 2,427 citations

A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.

1992 • 2,420 citations

Regulation of hypoxia-inducible factor 1α is mediated by an O ₂ -dependent degradation domain via the ubiquitin-proteasome pathway

1998 • 2,044 citations

Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions

1997 • 1,610 citations

Mutations in SDHD , a Mitochondrial Complex II Gene, in Hereditary Paraganglioma

2000 • 1,604 citations

HIF-1alpha is required for solid tumor formation and embryonic vascularization

1998 • 1,567 citations

Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer

2002 • 1,541 citations

Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel–Lindau protein

2000 • 1,527 citations

Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch

2002 • 1,512 citations

FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor

2002 • 1,472 citations

Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics.

2000 • 1,430 citations

FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity

2001 • 1,326 citations

HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression

2001 • 1,230 citations

Transcriptional Regulation of the Rat Vascular Endothelial Growth Factor Gene by Hypoxia

1995 • 1,087 citations

Gene Mutations in the Succinate Dehydrogenase Subunit SDHB Cause Susceptibility to Familial Pheochromocytoma and to Familial Paraganglioma

2001 • 1,082 citations

Hypoxia-inducible factor 1: master regulator of O2 homeostasis

1998 • 1,066 citations

Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth

1997 • 1,059 citations

Hypoxia Inducible Factor-α Binding and Ubiquitylation by the von Hippel-Lindau Tumor Suppressor Protein

2000 • 1,018 citations

Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation

2001 • 994 citations

Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor

1991 • 963 citations

Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor protein

2000 • 889 citations

Mutations in SDHC cause autosomal dominant paraganglioma, type 3

2000 • 877 citations

Loss of PTEN facilitates HIF-1-mediated gene expression

2000 • 824 citations

Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth.

2000 • 784 citations

Antioncogenes and human cancer.

1993 • 772 citations

Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase

1999 • 771 citations

Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia

2000 • 754 citations

HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation

2001 • 748 citations

Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling

2002 • 707 citations

Hypoxia-inducible Factor (HIF) Asparagine Hydroxylase Is Identical to Factor Inhibiting HIF (FIH) and Is Related to the Cupin Structural Family

2002 • 698 citations

Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL

2002 • 689 citations

HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors.

2001 • 688 citations

Binding of the von Hippel-Lindau Tumor Suppressor Protein to Elongin B and C

1995 • 672 citations

Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha

1998 • 653 citations

Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex

2000 • 635 citations

Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells

2001 • 602 citations

Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300

1999 • 583 citations

Inhibition of Transcription Elongation by the VHL Tumor Suppressor Protein

1995 • 571 citations

V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression.

1997 • 526 citations

Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α Subunit

1997 • 514 citations

Induction of HIF-1alpha in response to hypoxia is instantaneous.

2001 • 507 citations

Suppression of tumor growth through disruption of hypoxia-inducible transcription

2000 • 501 citations

The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins

1997 • 490 citations

Induction of HIF–1α in response to hypoxia is instantaneous

2001 • 416 citations

Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1

1999 • 387 citations

Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases and related enzymes

1999 • 382 citations

von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF

2001 • 374 citations

Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease

2001 • 364 citations

The R22X Mutation of the SDHD Gene in Hereditary Paraganglioma Abolishes the Enzymatic Activity of Complex II in the Mitochondrial Respiratory Chain and Activates the Hypoxia Pathway

2001 • 356 citations

Hypoxia-inducible Factor-1-mediated Expression of the 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) Gene

2002 • 341 citations

Transcriptional Response to Hypoxia in Human Tumors

2001 • 300 citations

Prolyl 4-hydroxylases and their protein disulfide isomerase subunit

1998 • 281 citations

Regulation of angiogenic growth factor expression by hypoxia, transition metals, and chelating agents

1995 • 274 citations

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

2000 • 265 citations

pVHL ₁₉ is a biologically active product of the von Hippel–Lindau gene arising from internal translation initiation

1998 • 248 citations

The von Hippel–Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal

1998 • 244 citations

Oxygen-regulated and Transactivating Domains in Endothelial PAS Protein 1: Comparison with Hypoxia-inducible Factor-1α

1999 • 241 citations

A second major native von Hippel–Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor

1998 • 226 citations

The VHL tumour-suppressor gene paradigm

1998 • 219 citations

The von Hippel–Lindau tumor suppressor protein

2001 • 208 citations

A Redox Mechanism Controls Differential DNA Binding Activities of Hypoxia-inducible Factor (HIF) 1α and the HIF-like Factor

2000 • 177 citations

Isoenzyme-specific regulation of genes involved in energy metabolism by hypoxia: similarities with the regulation of erythropoietin

1996 • 151 citations

VHL Induces Renal Cell Differentiation and Growth Arrest through Integration of Cell-Cell and Cell-Extracellular Matrix Signaling

2001 • 105 citations

The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis

2000 • 60 citations

Comparative Sequence Analysis of the VHL Tumor Suppressor Gene

2000 • 59 citations

Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy

1996 • 46 citations

The von Hippel-Lindau Gene Product Inhibits Renal Cell Apoptosis via Bcl-2-dependent Pathways

2001 • 45 citations

Selection of Mutant CHO Cells with Constitutive Activation of the HIF System and Inactivation of the von Hippel-Lindau Tumor Suppressor

2001 • 37 citations