HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing

By M. Ivan, K. Kondo, H. Yang, W. Kim, J. Valiando, M. Ohh, A. Salic, J. Asara, William Arbuthnot Sir Lane, W. Kaelin. Science, 2001

4,577 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2509bfd0e19da540665529f002a25bbd8bc8c183

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. M. V. Vander Heiden
4. Navdeep S. Chandel
5. Carlo Maria Croce
6. Ralph J. Deberardinis
7. Craig B. Thompson
8. M. C. Simon

In Molecular Biology

1. G. Semenza
2. C. V. Dang
3. M. V. Vander Heiden
4. Ralph J. Deberardinis
5. Navdeep S. Chandel
6. Craig B. Thompson
7. Carlo Maria Croce
8. M. C. Simon

Citations in the corpus

• The General Transcription Machinery and General Cofactors (2006, background): “…normaxia), in which recognition of the hydroxylated proline (mediated by prolyl-4-hydroxylase) by the hydrophobic pocket located at the β-domain of pVHL (Hon et al., 2002; Min et al., 2002) eventually leads to the ubiquitination and degradation of HIF-1α (Jaakkola et al., 2001; Ivan et al., 2001).”
• The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. (2002, background): “It has been recently shown that pVHL is a ubiquitin ligase (196, 276) that is involved in targeting of HIF1- for ubiquitin- and proteasome-mediated degradation (219, 220, 299) after specific recognition of oxygeninduced hydroxylated Pro residue (195, 197) (see also sect.”
• Differentiating the functional role of hypoxia‐inducible factor (HIF)‐1α and HIF‐2α (EPAS‐1) by the use of RNA interference: erythropoietin is a HIF‐2α target gene in Hep3B and Kelly cells (2004, background): “Both HIFα subunits are predominantly regulated at the protein level by oxygen-dependent prolyl hydroxylation, which leads to rapid pVHL (von Hippel-Lindau protein)-mediated ubiquitination and proteasomal degradation in normoxia (20, 21).”
• 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”
• HIF‐1α induces cell cycle arrest by functionally counteracting Myc (2004, background): “The VHL binding is controlled by hydroxylation of two proline residues in HIF- 1a: Pro-402 (Masson et al, 2001) and Pro-564 (Ivan et al, 2001; Jaakkola et al, 2001).”
• The role of hypoxia-inducible factors in tumorigenesis (2008, background): “Hydroxylation of conserved proline residues within the HIF-a ODD by prolyl-4hydroxylase domain (PHD)-containing proteins mediates pVHL binding and degradation.(20,21) Under hypoxia, HIF-a subunits are stabilized and translocate to the nucleus, where they heterodimerize with ARNT and bind to HREs loc”