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.

Mentioned in

WDR83

References in periodicals archive

By unraveling the precise molecular mechanism of BIM-EL stabilization by VHL and EglN3, we provide further insights into the chemoresistance that is typical of tumors lacking VHL or oxygen.

EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance.

Karolinska Institutet: Novel oxygen-sensing pathway identified that is lost in hypoxic tumors and in cells arising in the von Hippel-Lindau hereditary cancer syndrome causing cancer therapy resistance

It was also shown that KIF1B[beta] acts downstream from oxygen-dependent prolyl hidroxylase EGLN3 (or PHD3) to induce apoptosis.

Paragangliomas/pheochromocytomas: clinically oriented genetic testing

C-C chemokine receptor type 2 (CCR2 or CD192), TNF[alpha], inhibin beta A (INHBA), inducible nitric oxide synthase (iNOS), C-C chemokine receptor type 7 (CCR7), and Egl nine homolog 3 (EGLN3) were chosen as M1 markers.

Ubiquitous transgenic overexpression of C-C chemokine ligand 2: a model to assess the combined effect of high energy intake and continuous low-grade inflammation

elegans) (EGLN3); E1A binding protein p300 (EP300); and CREB binding protein (CREBBP), whereas miR-200b, miR-200c, and miR-429 target VHL; transcription elongation factor B (SIII), polypeptide 1 (15 kDa, elongin C) (TCEB1); EGLN1/3; EP300; and CREBBP.

MicroRNAs as regulators of signal transduction in urological tumors

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