Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.

By W. Kaelin, P. Ratcliffe. Molecules and Cells, 2008

3,162 citations recorded by the source corpus.

Subfields: Cancer Research, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/c0cbfaea5441a357db6e2f1f98028220ddabfd9b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Navdeep S. Chandel
2. G. Semenza
3. M. V. Vander Heiden
4. Ralph J. Deberardinis
5. Sophia Y. Lunt
6. David M. Sabatini
7. P. Ratcliffe
8. C. V. Dang

In Genetics

1. G. Semenza
2. Navdeep S. Chandel
3. V. Haase
4. M. V. Vander Heiden
5. Sophia Y. Lunt
6. P. Ratcliffe
7. Ralph J. Deberardinis
8. Lucas B. Sullivan

In Surgery

1. M. V. Vander Heiden
2. G. Semenza
3. Navdeep S. Chandel
4. Ralph J. Deberardinis
5. Sophia Y. Lunt
6. V. Haase
7. David M. Sabatini
8. Peggy P. Hsu

Citations in the corpus

• ROS Function in Redox Signaling and Oxidative Stress (2014, background): “HIFa is hydroxylated at proline residues by prolyl hydroxylases (PHDs) and these hydroxylated proline residues are then recognized by the E3 ubiquitin ligase von Hippel-Landau protein (pVHL), which targets HIFa to the proteasome [61].”
• Cancer cell metabolism: Warburg and beyond. (2008, background): “HIF initiates a transcriptional program that provides multiple solutions to hypoxic stress (reviewed in Kaelin and Ratcliffe, 2008).”
• Fundamentals of cancer metabolism (2016, background): “Some tumors display constitutive activation of HIF-1 under normoxic conditions through a variety of mechanisms, including (i) hyperactivation of mTORC1, (ii) loss of von Hippel–Lindau, (iii) accumulation of ROS, and (iv) accumulation of the TCA cycle metabolites succinate or fumarate due to cancer-s”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “HIF-1 is a heterodimer composed of HIF-1α and HIF-1β (ARNT) subunits, and the biological activity of HIF-1 is determined by presence of the HIF-1α subunit, whose stability is regulated by oxygen levels (Kaelin & Ratcliffe 2008).”
• Regulation of erythropoiesis by hypoxia-inducible factors (2013, background): “CBP/p300 recruitment and results in increased HIF target gene expression under hypoxia.(86) In the kidney, FIH has been detected in REPC, podocytes and in the distal tubule.”
• HECT and RING finger families of E3 ubiquitin ligases at a glance (2012, background): “A key mediator of this is the hypoxia-inducible factor (HIF) family of transcription factors that induce transcription of genes involved in bioenergetics, cell growth and angiogenesis (Kaelin and Ratcliffe, 2008; Majmundar et al., 2010).”
• Metabolic regulation of hematopoietic stem cells in the hypoxic niche. (2011, background): “Under normoxic conditions, HIF-1a is hydroxylated at proline (Pro) 402 and/or 564 in the O2-dependent degradation (ODD) domain (Kaelin and Ratcliffe, 2008) by three prolyl hydroxylases, PHD1–3, which require O2, Fe 2+, 2-oxoglutarate (2-OG; a-ketoglutarate), and ascorbate for enzymatic activity…”
• Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014, background): “Visiting again O2 sensing by the HIF system, the Km towards O2 of PHD is 100 M [30], much higher than the endogenous concentration of O2 (approximately 30 M), and so the HIF system responds to O2 changes in the operational O2 concentration range in vivo.”
• Reactive oxygen species in cancer (2010, background): “Under normal growth conditions HIF-1 is regulated by oxygen-dependent prolyl hydroxylases (PHDs) and the VHL ubiquitin ligase, which promote its proteosomal degradation [201].”
• Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy (2012, background): “A principal mechanism by which O2 regulates HIF activity is through proline and asparagine hydroxylation [3, 4].”