Characterisation of nematode prolyl 4-hydroxylase collagen.
Publications; Expression of PHD (prolyl hydroxylase)-1, PHD-2 and PHD3 is upregulated in the nucleus and cytoplasm in neoplastic breast disease and nuclear PHD expression is associated with the estrogen receptor in invasive breast carcinomas.
PURPOSE: To discover novel small molecules that inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD), a key enzyme that regulates the posttranslational stability and hence activity of HIF.
Webb TM, Hagen T, Feng Y, Longmore GD and Sharp TV.The Tumour Suppressor Gene Product LIMD1 binds the HIF1-alpha Prolyl Hydroxylases 1, 2 and 3 and down regulates the hypoxic response in vivo.
In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase Contents 1 The hypoxia response.
Human and other animal cells deploy three closely related dioxygenases (PHD 1, 2 and 3) to signal oxygen levels by catalysing oxygen regulated prolyl hydroxylation of the transcription factor HIF. The discovery of the HIF prolyl-hydroxylase (PHD) enzymes as oxygen sensors raises a key question as to the existence and nature of non-HIF substrates, potentially transducing other biological.
Abstract: Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1 stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1 levels for therapeutic applications.
Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). domain (8); this modification blocks interaction of HIF-1 hydroxylase and PHD inhibitors (Fig. 1 with the CBP p300 coactivator, thereby disabling HIF-mediated transcription.