EGLN3

(redirected from PHD3)

EGLN3

A gene on chromosome 14q13.1 that encodes a cellular oxygen sensor that catalyses, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. EGLN3 limits physiologic activation of HIF during hypoxia and hydroxylates PKM2, limiting glycolysis. Under normoxia, EGLN3: hydroxylates and regulates the stability of ADRB2; regulates cardiomyocyte and neuronal apoptosis; inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex in cardiac myocytes; has an NGF-induced pro-apoptotic effect on neurons by regulating CASP3 activity; and is essential for hypoxic regulation of neutrophilic inflammation.

EGLN2 hydroxylates a specific proline found in each oxygen-dependent degradation (ODD) domains—N-terminal (NODD) and C-terminal (CODD)—of HIF1A; hydroxylated HIFs are then targeted for proteasomal degradation by the von Hippel-Lindau ubiquitination complex. During hypoxia, the hydroxylation reaction is attenuated, allowing HIFs to escape degradation, resulting in translocation to the nucleus, heterodimerisation with HIF1B and increased expression of hypoxy-inducible genes.
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Cullen, PhD [2]; Enver Holder-Hayes, MPH [2]; Carolyn Reyes-Guzman, PhD3; Ahmed Jamal, MBBS1; Linda Neff, PhD [1]; Brian A.
Naseem Ahmed, MCPS, FCPS [1], Kiran Naseem, MS(Economics) [2], Muhammad Rafiq, PhD3
Duodenal Regnase-1 regulates the expression of prolyl-hydroxylase-domain-containing protein 3 (PHD3) by targeting its 3' UTRs.
In addition to signal transduction via HIFs, PHD3 has been shown to stabilize the tight junction protein occludin in IECs by preventing its interaction with the E3 ligase Itch in a hydroxylase-independent manner [79].
Hillemann et al., "Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions," Journal of Leukocyte Biology, vol.
P Skowno, PhD1, W Derman, MBChB, FFIMS, PhD2, D J Stein, MBChB, FRCPC, PhD3, C E Draper, PhD1
The presence of OS-9 promotes interaction of HIF-1[alpha] with prolylhydroxylase domain proteins PHD2 or PHD3, leading to hydroxylation and Von Hippel-Lindau (VHL) binding.
The cases PHD1, PHD2, and PHD3 with a risk for manifest chorea within little time presented with P2 latency in the upper normal limits.
Annie LeBrun, BSc, [1] Ghayda Hassan, PhD, [1] Mylene Boivin, PhD,1 Sarah-Louise Fraser, PhD, [2] Sarah Dufour, PhD, [2] Chantal Lavergne, PhD3
It was also shown that KIF1B[beta] acts downstream from oxygen-dependent prolyl hidroxylase EGLN3 (or PHD3) to induce apoptosis.
His laboratory has identified a protein called PhD3 that could be a particularly attractive target.