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lüll Reciprocal influence of the p53 and the hypoxic pathways Sermeus A; Michiels CCell Death Dis 2011[May]; 2 (ä): e164When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1alpha stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1alpha and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed.|Animals[MESH]|Cell Death[MESH]|Cell Hypoxia[MESH]|Cell Survival[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit/metabolism[MESH]|Hypoxia/*metabolism/pathology[MESH]|Mutation[MESH]|Tumor Suppressor Protein p53/genetics/*metabolism[MESH] |