Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation

By P. Jaakkola, D. Mole, Ya-min Tian, Michael I. Wilson, J. Gielbert, S. Gaskell, A. Kriegsheim, H. Hebestreit, Mridul Mukherji, Christopher J. Schofield and 3 more. Science, 2001

4,904 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/15393e2ed24afe67204248f424f85a903bdec420

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. G. Semenza
2. C. V. Dang
3. Carlo Maria Croce
4. M. C. Simon
5. W. Kaelin
6. Craig B. Thompson
7. George A. Calin
8. P. Schumacker

In Molecular Biology

1. G. Semenza
2. C. V. Dang
3. Carlo Maria Croce
4. W. Kaelin
5. M. C. Simon
6. Craig B. Thompson
7. George A. Calin
8. P. Schumacker

In Physiology

1. G. Semenza
2. Roland H. Wenger
3. M. C. Simon
4. P. Trayhurn
5. P. Schumacker
6. R. Guzy
7. Ana Samimi
8. Robert B Rucker

Citations in the corpus

• Chapter 3 – A Profile of the Metabolic Responses to Anoxia in Marine Invertebrates (2002, background): “The most recent research suggests that the oxygen sensor is a prolyl hydroxylase enzyme, which oxidatively modifies (hydroxylates) a highly conserved proline residue found in the oxygen-dependent degradation domain of HIF-1, the central transcription factor involved in the regulation of gene transcr”
• The Roles of NRF2 in Modulating Cellular Iron Homeostasis (2017, background): “As was observed in renal cell carcinoma, HIF2a, but not HIF1a, confers tumorigenic potential upon inactivation of the von Hippel-Lindau tumor suppressor (128).”
• Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related Enzymes (2004, background): “A prolyl 4-hydroxylase plays a key role in targeting HIFα for degradation on the basis of evidence indicating that Pro 564 of HIFα is hydroxylated in an oxygen-, Fe(II)-, and αKG-dependent reaction (Ivan et al., 2001; Jaakkola et al., 2001).”
• Cellular adaptation to hypoxia: O2‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O2‐regulated gene expression (2002, background): “As discovered by Maxwell and co-workers (23), this degradation is mediated by pVHL, binding to the hydroxylated but not to the nonhydroxylated HIF-1 ODD domain (51, 52).”
• Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. (2005, background): “In particular, elevated levels al., 2001; Jaakkola et al., 2001; Yu et al., 2001).”
• Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. (2002, background): “The VHL gene resides on chromosome 3p25, and individuals with VHL disease are is governed by oxygen-dependent hydroxylation of conserved proline residues in HIF by members of the Egl9 family (Bruick germline VHL / heterozygotes. Tumors develop in this setting when the remaining wild-type VHL allele ”