HIF-1 as a target for drug development

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

Hypoxia — a key regulatory factor in tumour growth

2002 • 4,942 citations

Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis

1992 • 4,631 citations

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

2001 • 4,537 citations

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

2001 • 3,215 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

Cellular and developmental control of O₂ homeostasis by hypoxia-inducible factor 1α

1998 • 2,392 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

Purification and Characterization of Hypoxia-inducible Factor 1

1995 • 2,010 citations

New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway

1999 • 1,972 citations

HIF-1α Is Essential for Myeloid Cell-Mediated Inflammation

2003 • 1,909 citations

Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.

1994 • 1,821 citations

Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor

2002 • 1,717 citations

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

1997 • 1,610 citations

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

1998 • 1,567 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

The unique physiology of solid tumors: opportunities (and problems) for cancer therapy.

1998 • 1,506 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

Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.

1997 • 1,325 citations

SCF and Cullin/RING H2-Based Ubiquitin Ligases

1999 • 1,249 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

Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit

1996 • 1,172 citations

Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin

2002 • 1,147 citations

Dimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1

1996 • 1,081 citations

Regulation of the Erythropoietin Gene: Evidence That the Oxygen Sensor Is a Heme Protein

1988 • 1,042 citations

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

2000 • 1,018 citations

A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development

1997 • 1,004 citations

Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization

2002 • 982 citations

Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

2001 • 981 citations

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

2000 • 889 citations

Signal transduction to hypoxia-inducible factor 1

2002 • 843 citations

Loss of PTEN facilitates HIF-1-mediated gene expression

2000 • 824 citations

Stabilization of wild-type p53 by hypoxia-inducible factor 1α

1998 • 818 citations

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis

2002 • 785 citations

Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT

1997 • 778 citations

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

1999 • 771 citations

2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF

2003 • 713 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

Regulation and Destabilization of HIF-1α by ARD1-Mediated Acetylation

2002 • 693 citations

Hsp90 inhibitors as novel cancer chemotherapeutic agents

2002 • 673 citations

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

1995 • 672 citations

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

2001 • 666 citations

Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.

1999 • 645 citations

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

2000 • 635 citations

Hsp90 Regulates a von Hippel Lindau-independent Hypoxia-inducible Factor-1α-degradative Pathway

2002 • 633 citations

Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α

1997 • 605 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

Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.

1998 • 572 citations

Inhibition of Transcription Elongation by the VHL Tumor Suppressor Protein

1995 • 571 citations

Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha /ARNT

1998 • 561 citations

Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1.

2001 • 550 citations

Insulin Stimulates Hypoxia-inducible Factor 1 through a Phosphatidylinositol 3-Kinase/Target of Rapamycin-dependent Signaling Pathway

2002 • 527 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

Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway

1997 • 510 citations

Suppression of tumor growth through disruption of hypoxia-inducible transcription

2000 • 501 citations

Induction of Vascular Endothelial Growth Factor by Hypoxia Is Modulated by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Ha-ras-Transformed Cells Through a Hypoxia Inducible Factor-1 Transcriptional Element

1997 • 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

Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways

1997 • 470 citations

TOR signalling and control of cell growth

1997 • 458 citations

YC-1: A Potential Anticancer Drug Targeting Hypoxia-Inducible Factor 1

2003 • 454 citations

Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway.

2002 • 448 citations

How the Cyclin Became a Cyclin

1999 • 441 citations

Relation of vascular proliferation to tumor growth.

1976 • 413 citations

Molecular mechanisms of vasculogenesis and embryonic angiogenesis

1997 • 409 citations

YC-1, a novel activator of platelet guanylate cyclase

1994 • 401 citations

Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2

1998 • 377 citations

The regulated expression of erythropoietin by two human hepatoma cell lines.

1987 • 374 citations

Redox-Regulated Recruitment of the Transcriptional Coactivators CREB-Binding Protein and SRC-1 to Hypoxia-Inducible Factor 1α

2000 • 371 citations

Inhibitory PAS Domain Protein (IPAS) Is a Hypoxia-inducible Splicing Variant of the Hypoxia-inducible Factor-3α Locus

2002 • 353 citations

Angiogenesis Is Induced in a Rabbit Model of Hindlimb Ischemia by Naked DNA Encoding an HIF-1α/VP16 Hybrid Transcription Factor

2000 • 321 citations

Proteolysis and the cell cycle: with this RING I do thee destroy

2000 • 308 citations

Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells.

2002 • 296 citations

p53 Inhibits Hypoxia-inducible Factor-stimulated Transcription

1998 • 284 citations

Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway.

2001 • 269 citations

Role of Prolyl Hydroxylation in Oncogenically Stabilized Hypoxia-inducible Factor-1α

2002 • 260 citations

Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice.

1991 • 250 citations

The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation.

2003 • 248 citations

Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression.

1996 • 240 citations

2-Methoxyestradiol: an endogenous antiangiogenic and antiproliferative drug candidate.

2000 • 235 citations

MAP kinases and hypoxia in the control of VEGF expression.

2000 • 223 citations

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803

2002 • 211 citations

Involvement of Hypoxia-Inducible Factor 1 in Human Cancer.

2002 • 206 citations

Hypoxia-mediated stimulation of carcinoma cell invasivenessvia upregulation of urokinase receptor expression

1999 • 195 citations

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

2000 • 177 citations

Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1α (HIF-1α): Role of Cytoplasmic Trapping of HIF-2α

2003 • 170 citations

MAPK and Akt Act Cooperatively but Independently on Hypoxia Inducible Factor-1α in rasV12 Upregulation of VEGF

2001 • 160 citations

Gene transfer of antisense hypoxia inducible factor-1 α enhances the therapeutic efficacy of cancer immunotherapy

2001 • 144 citations

Hypoxia Up-regulates Expression of Peroxisome Proliferator-activated Receptor γ Angiopoietin-related Gene (PGAR) in Cardiomyocytes: Role of Hypoxia Inducible Factor 1α

2002 • 137 citations

Characterization of an Oxygen/Redox-Dependent Degradation Domain of Hypoxia-Inducible Factor α (HIF-α) Proteins

1999 • 136 citations

Hypoxia-inducible factor-1α is regulated at the post-mRNA level

1997 • 134 citations

Inhibition of Collagen Synthesis With Prolyl 4-Hydroxylase Inhibitor Improves Left Ventricular Function and Alters the Pattern of Left Ventricular Dilatation After Myocardial Infarction

2001 • 129 citations

Molecular Mechanism of Hypoxia-inducible Factor 1α-p300 Interaction

2001 • 125 citations

Lack of Evidence for the Involvement of the Phosphoinositide 3-Kinase/Akt Pathway in the Activation of Hypoxia-inducible Factors by Low Oxygen Tension

2002 • 116 citations

Activated pp60c-Src Leads to Elevated Hypoxia-inducible Factor (HIF)-1α Expression under Normoxia

2002 • 115 citations

Studying interactions of four proteins in the yeast two-hybrid system: Structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein

1999 • 101 citations

Microtubule Disruption Utilizes an NFκB-dependent Pathway to Stabilize HIF-1α Protein

2003 • 98 citations

The pVHL-HIF-1 system

2001 • 95 citations

Identification and expression of alternatively spliced aryl hydrocarbon nuclear translocator 2 (ARNT2) cDNAs from zebrafish with distinct functions

2000 • 94 citations

A new HIF-1 alpha variant induced by zinc ion suppresses HIF-1-mediated hypoxic responses

2001 • 88 citations

A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1α gene

2002 • 76 citations

The farnesyltransferase inhibitor L744,832 reduces hypoxia in tumors expressing activated H-ras.

2001 • 71 citations

Harnessing the Response to Tissue Hypoxia HIF-1α and Therapeutic Angiogenesis

2002 • 64 citations

Regulatory elements of the erythropoietin gene

1991 • 61 citations

Gene expression profiles in human cardiac cells subjected to hypoxia or expressing a hybrid form of HIF-1α

2002 • 59 citations

A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts

2001 • 59 citations

Cell-specificity and signaling pathway of endothelin-1 gene regulation by hypoxia

1995 • 57 citations

Hypoxic Induction of the Hypoxia-Inducible Factor Is Mediated via the Adaptor Protein Shc in Endothelial Cells

2002 • 53 citations

A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1α gene

2002 • 37 citations

Efficacy of the quinocarmycins KW2152 and DX-52-1 against human melanoma lines growing in culture kand in mice.

1995 • 25 citations

Regulation of the Hypoxia-Inducible Factor-1α

2002 • 20 citations

Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies

2001 • 14 citations