Abstract
Oxygen-deprived regions of a solid tumor can induce tumor suppressor p53 expression and hence select for p53-mutant tumor cells with diminished apoptotic potential. It has been proposed that the hypoxia-inducible factor-1 (HIF-1) alpha subunit binds to p53 and protects it from proteasomal degradation. However, we found that hypoxic conditions that strongly induce HIF-1-dependent endogenous gene expression as well as HIF-1alpha protein neither induce p53-dependent gene expression nor p53 protein. The iron chelator deferoxamine induced both HIF-1alpha and p53, but p53 up-regulation could still be detected in HIF-1alpha-deficient cells, suggesting that mechanisms other than HIF-1alpha activation contribute to oxygen-regulated p53 induction.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Aryl Hydrocarbon Receptor Nuclear Translocator
-
Cell Hypoxia*
-
DNA-Binding Proteins / metabolism*
-
Deferoxamine / pharmacology
-
Gene Expression Regulation, Neoplastic*
-
Genes, p53*
-
Humans
-
Hypoxia-Inducible Factor 1
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Mice
-
Nuclear Proteins / metabolism*
-
Receptors, Aryl Hydrocarbon*
-
Transcription Factors / metabolism
-
Tumor Cells, Cultured
-
Up-Regulation
Substances
-
ARNT protein, human
-
Arnt protein, mouse
-
DNA-Binding Proteins
-
HIF1A protein, human
-
Hif1a protein, mouse
-
Hypoxia-Inducible Factor 1
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Nuclear Proteins
-
Receptors, Aryl Hydrocarbon
-
Transcription Factors
-
Aryl Hydrocarbon Receptor Nuclear Translocator
-
Deferoxamine