C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.

By A. C. Epstein, J. Gleadle, Luke A. McNeill, K. Hewitson, J. O'rourke, D. Mole, Mridul Mukherji, E. Metzen, Michael I. Wilson, A. Dhanda and 10 more. Cell, 2001

3,389 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/b895aa050f770137e8e1736499241be30e8e47a0

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In Cancer Research

1. G. Semenza
2. W. Kaelin
3. M. C. Simon
4. Navdeep S. Chandel
5. J. Pouysségur
6. Amato J. Giaccia
7. P. Schumacker
8. P. Ratcliffe

In Molecular Biology

1. G. Semenza
2. W. Kaelin
3. M. C. Simon
4. P. Schumacker
5. Navdeep S. Chandel
6. P. Ratcliffe
7. J. Pouysségur
8. Amato J. Giaccia

In Physiology

1. G. Semenza
2. Amato J. Giaccia
3. M. C. Simon
4. Roland H. Wenger
5. W. Kaelin
6. P. Ratcliffe
7. P. Schumacker
8. R. Guzy

Citations in the corpus

• HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. (2007, neutral): “…to CoCl 2 , desferrioxamine (DFX), or dimethyloxalylglycine (DMOG), which are inducers of HIF-1 a expression that inhibit hydroxylase activity (Epstein et al., 2001; Jaakkola et al., 2001) and thereby increase the expression of mRNAs encoded by HIF-1 target genes such as GLUT1 (Figures 1D and…”
• Molecular basis of the VHL hereditary cancer syndrome (2002, background): “The gene is relatively small, consisting of three exons, and is conserved in rodents, flies and worm”
• Heterozygous Deficiency of PHD2 Restores Tumor Oxygenation and Inhibits Metastasis via Endothelial Normalization (2009, neutral): “Consistent with its hypoxia inducibility (Epstein et al., 2001; Marxsen et al., 2004), PHD3 mRNA levels in PHD2 +/À mice were downregulated in tumors and tumor ECs freshly isolated from tumors and directly used for analysis (Figures S3I and S3J).”
• Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. (2005, background): “, 2003), so it has been proposed that PHDs function as O2 sensors because the decreasing availability of O2 during hypoxia could limit their ability to hydroxylate HIF (Hagen et al., 2003; Epstein et al., 2001).”
• Hypoxia-Inducible Factor-1 (HIF-1) (2006, neutral): “The absolute requirement of oxygen as a cosubstrate suggests PHDs as the oxygen sensor in cells (Epstein et al., 2001).”
• Hypoxia signalling in cancer and approaches to enforce tumour regression (2006, background): “The first are referred to as prolyl hydroxylase domain (PHD) protein”
• HIF‐1α induces cell cycle arrest by functionally counteracting Myc (2004, background): “These prolines are modified in normoxia by the HIF prolyl-4-hydroxylases that require oxy- gen, iron, and 2-oxoglutarate as cofactors (Bruick and McKnight, 2001; Epstein et al, 2001).”
• FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. (2002, background): “Like these enzymes, the HIF prolyl hydroxylase enzymes use Fe(II) to bind O2 to hydroxylate both 2-oxoglutarate and the target proline residue (Bruick and McKnight 2001; Epstein et al. 2001).”