Up-regulation of hypoxia-inducible factor-1 alpha is not sufficient for hypoxic/anoxic p53 induction

Oxygen-deprived regions of a solid tumor can induce tumor suppressor p53 ex pression and hence select for p53-mutant tumor cells with diminished apopto tic potential, It has been proposed that the hypoxia-inducible factor-1 (HI F-1) alpha subunit binds to p53 and protects it from proteasomal degradatio n. However, we found that hypoxic conditions that strongly induce HIF-1-dep endent endogenous gene expression as well as HIF-1 alpha protein neither in duce p53-dependent gene expression nor p53 protein, The iron chelator defer oxamine induced both HIF-1 alpha and p53, but p53 up-regulation could still be detected in HIF-1 alpha-deficient cells, suggesting that mechanisms oth er than HIF-1 alpha activation contribute to oxygen-regulated p53 induction .