HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation

By F. Yu, S. White, Quan Zhao, F. Lee. Proceedings of the National Academy of Sciences of the United States of America, 2001

776 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/9b33f746394bba738a28b1304264e1f13279d1ca

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. M. C. Simon
3. W. Kaelin
4. Amato J. Giaccia
5. Craig B. Thompson
6. Eyal Gottlieb
7. Roland H. Wenger
8. Cormac T. Taylor

In Molecular Biology

1. G. Semenza
2. M. C. Simon
3. W. Kaelin
4. Craig B. Thompson
5. Amato J. Giaccia
6. Eyal Gottlieb
7. Roland H. Wenger
8. C. Pickart

In Surgery

1. G. Semenza
2. K. Guan
3. M. C. Simon
4. Craig B. Thompson
5. Kyle D Mansfield
6. W. Kaelin
7. William Y. Kim
8. Amato J. Giaccia

Citations in the corpus

• Prolyl 4-Hydroxylase (2003, background): “The mechanism of the hypoxia response 18 pathway, which has only recently been resolved, entails a significant regulatory role for 4-hydroxyproline residues (Ivan et al. 2001, Jaakkola et al. 2001, Yu et al. 2001).”
• Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. (2005, neutral): “…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., 2001; Jaakkola et al., 2001; Yu et al., 2001).”
• Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin (2002, background): “Exposure of the cells to hypoxia or to the PHD inhibitor CoCl2 (unpublished results) led to significant stabilization of HIF-1, which is consistent with the model that the ODD domain, and specifically the region surrounding Pro- 564, confers instability on the HIF-1 protein at normal oxygen tensions”
• HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. (2007, neutral): “Under aerobic conditions, HIF-1 a and HIF-2 a are subjected to prolyl hydroxylation by enzymes that utilize O 2 as a substrate (Ivan et al., 2001; Jaak-kola et al., 2001; Yu et al., 2001).”
• 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 HIF2α Is Sufficient to Suppress pVHL-Defective Tumor Growth (2003, background): “Hydroxylation of HIF1a Pro564 or HIF2a Pro531 generates a pVHL-binding site (Ivan et al. 2001; Jaakkola et al. 2001; Yu et al. 2001).”
• Cellular adaptation to hypoxia: O2‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O2‐regulated gene expression (2002, background): “To the surprise of all researchers involved in the hunt for the oxygen sensor, this modification turned out to be the hydroxylation of two proline residues (Pro402 and Pro564) by a prolyl-4-hydroxylase, similar to the proline modification known from the collagens (51, 52, 54, 55).”
• 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 ”
• HECT and RING finger families of E3 ubiquitin ligases at a glance (2012, background): “VHL mediates recognition of HIF1-a proteins by binding to hydroxylated prolines, a modification that is catalyzed by the oxygen-sensing prolyl hydroxylases (PHDs) (Jaakkola et al., 2001; Ohh, 2006; Yu et al., 2001).”