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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
TLDR
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. Expand
C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation
TLDR
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. Expand
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
TLDR
HIF plays a central role in the transcriptional response to changes in oxygen availability and is modulated by FIH1-mediated asparagine hydroxylation, and HIF-modulatory drugs are now being developed for diverse diseases. Expand
Regulation of angiogenesis by hypoxia: role of the HIF system
TLDR
The role of HIF in developmental, adaptive and neoplastic angiogenesis, and the implications of oncogenic activation of extensive, physiologically interconnected hypoxia pathways for the tumor phenotype are discussed. Expand
Hypoxia-inducible expression of tumor-associated carbonic anhydrases.
TLDR
A new class of HIF-1-responsive gene is defined, the activation of which has implications for the understanding of hypoxic tumor metabolism and which may provide endogenous markers for tumor hypoxia. Expand
Oxygen sensing by HIF hydroxylases
TLDR
The transcription factor HIF (hypoxia-inducible factor) has a central role in oxygen homeostasis in animals ranging from nematode worms to man and is regulated by an unprecedented signalling mechanism that involves post-translational hydroxylation. Expand
Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor*
TLDR
It is shown using suppression by small interference RNA that each of the three PHD isoforms contributes in a non-redundant manner to the regulation of both Hif-1α and HIF-2α subunits and that the contribution of each PHD under particular culture conditions is strongly dependent on the abundance of the enzyme. Expand
Contrasting Properties of Hypoxia-Inducible Factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-Associated Renal Cell Carcinoma
TLDR
HIF-α isoform-specific transcriptional selectivity was matched by differential effects on the growth of RCC as tumor xenografts, with HIF-1α retarding and Hif-2α enhancing tumor growth. Expand
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
TLDR
It is shown that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (Hif-1α+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1 α genes (HIF- 1α−/−), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Expand
High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq.
TLDR
Using chromatin immunoprecipitation linked to high throughput sequencing, HIF-binding sites across the genome are identified, indicating that these sites operate over long genomic intervals, and epigenetic regulation of chromatin may have an important role in defining the response to hypoxia. Expand
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