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

摘要: Although hypoxia (lack of oxygen in body tissues) is perhaps the most physiological inducer wild-type p53 gene, mechanism this induction unknown. Cells may detect low levels through a haem-containing sensor protein. The hypoxic state can be mimicked by using cobalt chloride and iron chelator desferrioxamine: like hypoxia, desferrioxamine activate hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulates transcription several genes that are associated with hypoxia. Here we show these treatments induce accumulation HIF-1alpha-dependent stabilization Induction does not occur either mutant hepatoma cell line unable to HIF-1alpha or embryonic stem cells derived from mice lacking HIF-1beta. found immunoprecipitates MCF7 express have been exposed desferrioxamine. Similarly, anti-haemagglutinin lysates normoxic PC3M had co-transfected haemagglutinin-tagged also contain p53. Transfection p53-dependent reporter plasmid increases amount endogenous Our results suggest transcriptionally active achieved as result its association HIF-1alpha.