Journal ArticleDOI
Signal transduction to hypoxia-inducible factor 1.
TLDR
In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.About:
This article is published in Biochemical Pharmacology.The article was published on 2002-09-01. It has received 859 citations till now. The article focuses on the topics: Signal transduction & Receptor tyrosine kinase.read more
Citations
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Journal ArticleDOI
Signaling pathways in renal cell carcinoma.
TL;DR: The state of knowledge about signaling pathways in RCC is summarized and the known genetic and epigenetic alterations that underlie dysregulation of these pathways are discussed.
Journal ArticleDOI
Radiation-induced lung injury (RILI)
TL;DR: Current understanding of the pathological and molecular consequences of lung exposure to ionizing radiation, and pharmaceutical interventions that may be beneficial in the prevention or curtailment of RILI, and therefore enable a more durable therapeutic tumor response are summarized.
Journal ArticleDOI
HIFs and tumors--causes and consequences.
TL;DR: In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.
Journal ArticleDOI
Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis.
TL;DR: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
Journal ArticleDOI
A novel role of hypoxia-inducible factor in cobalt chloride-and hypoxia-mediated expression of IL-8 chemokine in human endothelial cells
TL;DR: The data indicate that hypoxia-induced signaling in vascular endothelium for transcriptional activation of IL-8 involves PI3K/Akt, p38 MAPK, and HIF-1α, which may possibly ameliorate inflammation associated with Hypoxia in pathological diseases.
References
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Journal ArticleDOI
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
Journal ArticleDOI
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Patrick H. Maxwell,Michael S. Wiesener,Gin-Wen Chang,Steven C. Clifford,Emma C. Vaux,Matthew Edward Cockman,Charles C. Wykoff,Christopher W. Pugh,Eamonn R. Maher,Peter J. Ratcliffe,Peter J. Ratcliffe +10 more
TL;DR: It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.
Journal ArticleDOI
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Journal ArticleDOI
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Andrew C. R Epstein,Jonathan M. Gleadle,Luke A. McNeill,Kirsty S. Hewitson,J F O'Rourke,David R. Mole,Mridul Mukherji,Eric Metzen,Michael A Wilson,Anu Dhanda,Ya-Min Tian,Norma Masson,Donald L. Hamilton,Panu Jaakkola,Robert Barstead,Jonathan Hodgkin,Patrick H. Maxwell,Christopher W. Pugh,Christopher J. Schofield,Peter J. Ratcliffe +19 more
TL;DR: Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.