Faculty Opinions recommendation of HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

By P. O’Farrell. 2001

863 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/29722e33973a49c6065ed56f414b1a1b445ddce4

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Citations in the corpus

2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. (2003, background): “However, the preproline residues 402 and 564 (Ivan et al., 2001; Jaakkola et al., S I G N I F I C A N C E”
Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. (2005, positive): “Many hypoxic transcriptional responses are mediated by the hypoxia inducible factors (HIFs) whose activity is regulated mainly through the stability of their α subunits, which are hydroxylated on prolines within their oxygen-dependent degradation domains (ODDs) under normoxic conditions (Ivan et al.”
Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases (2011, positive): “HIF-1a is a transcription factor whose function is linked to metabolism, angiogenesis and tumorigenesis, and whose protein level is downregulated under normoxic conditions by PHD-mediated hydroxylation and subsequent hydroxylation-targeted ubiquitination (Bruick and McKnight, 2001; Epstein et al., 2”
Hypoxia-Inducible Factor-1 (HIF-1) (2006, neutral): “In the presence of oxygen, the PHDs are active and hydroxylate the prolines of HIF-1 , constituting a recognition signal for binding of pVHL and subsequent ubiquitination, followed by degradation of HIF-1 (Ivan et al., 2001; Jaakkola et al., 2001).”
The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche (2010, background): “Hif-1a undergoes hydroxylation, followed by ubiquitination and degradation during normoxia in most cells (Ivan et al., 2001; Jaakkola et al., 2001; Kamura et al., 2000; Maxwell et al., 1999; Salceda and Caro, 1997).”
RING domain E3 ubiquitin ligases. (2009, background): “Indeed, the vast majority of CRL substrates are targeted to their respective ligase by a covalent modification, including glycosylation (117) and proline hydroxylation (118, 119).”
Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. (2005, background): “Hydroxylation at proline residues allows for HIF-1α to interact with the von HippelLindau tumor suppressor protein (pVHL), which has ubiquitin ligase activity and leads to degradation of HIF-1α (Ivan et al., 2001; Jaakkola et al., 2001).”
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation (2003, neutral): “To stabilize transfected HIF- protein under normoxia, two hydroxylated prolines in both HIF-1 and HIF-2 oxygen-dependent-degradation domains (41, 43, 65) were mutated to alanine (Fig.”
Oxidative Stress and Oxidative Damage in Carcinogenesis (2010, background): “The oxygendependent degradation of HIF-1a is sensed by prolyl hydroxylases (PHDs), and following hydroxylation, HIF-1a is recognized by the von Hippel-Lindau (pVHL, the E3 ubiquitin protein ligase) and undergoes proteasomal degradation (Ivan et al. 2001).”
Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia (2006, background): “(2001), we now know that prolyl hydroxylase requires oxygen as a substrate for hydroxylation of HIF-1α (Ivan et al. 2001; Jaakkola et al. 2001).”