Stabilization of wild-type p53 by hypoxia-inducible factor 1α

@article{An1998StabilizationOW,
  title={Stabilization of wild-type p53 by hypoxia-inducible factor 1$\alpha$},
  author={Won Gun An and Meera Kanekal and M. Celeste Simon and Emin Maltepe and Mikhail V. Blagosklonny and Len Neckers},
  journal={Nature},
  year={1998},
  volume={392},
  pages={405-408}
}
Although hypoxia (lack of oxygen in body tissues) is perhaps the most physiological inducer of the wild-type p53 gene, the mechanism of this induction is unknown. Cells may detect low oxygen levels through a haem-containing sensor protein. The hypoxic state can be mimicked by using cobalt chloride and the iron chelator desferrioxamine: like hypoxia, cobalt chloride and desferrioxamine activate hypoxia-inducible factor 1α (HIF-1α) (ref. 6), which stimulates the transcription of several genes… 
p53 Inhibits Hypoxia-inducible Factor-stimulated Transcription*
TLDR
It is demonstrated that p53 represses HIF-1-stimulated transcription, and data support a model in which stoichiometric binding of p53 to a HIF/p300 transcriptional complex mediates inhibition of HIF activity.
for Hypoxic / Anoxic p 53 Induction Is Not Sufficient α Up-Regulation of Hypoxia-inducible Factor-1 Updated
TLDR
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In Cultured Astrocytes, p53 and MDM2 Do Not Alter Hypoxia-inducible Factor-1α Function Regardless of the Presence of DNA Damage*
TLDR
Data strongly suggest that p53 and MDM2 do not influence the hypoxia-induced transactivation of HIF-1α targets, regardless of p53 activation, in primary astrocytes.
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
TLDR
It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.
HIF-1α antagonizes p53-mediated apoptosis by triggering HIPK2 degradation
TLDR
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Jab1 Interacts Directly with HIF-1α and Regulates Its Stability*
TLDR
Jab1 should be considered as a novel regulator of HIF-1α stability via direct interaction, as it led to increase the expression of VEGF, a major Hif-1 target gene.
The hypoxia-inducible factor-1α is a negative factor for tumor therapy
TLDR
Hypoxia-independent basal HIF-1α expression in tumor cells, as known from untransformed embryonic stem cells, is sufficient to induce target gene expression, probably including DNA double-strand break repair enzymes.
p53 cannot be induced by hypoxia alone but responds to the hypoxic microenvironment
TLDR
The results suggest that, although hypoxia induces p53 accumulation in vivo, secondary effects such as acidosis caused by a hypoxic Pasteur effect (instead of low O2 by itself) are necessary for p 53 accumulation.
HIF-transcribed p53 chaperones HIF-1α
TLDR
A novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter is demonstrated, which has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.
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