Crosstalk between Mdm2, p53 and HIF1-α: distinct responses to oxygen stress and implications for tumour hypoxia.

ABSTRACT

The E3 ubiquitin ligase Mdm2 regulates two transcription factors, p53 and HIF1α, which appear to be tailored towards different and specific roles within the cell, the DNA damage and hypoxia responses, respectively. However, evidence increasingly points towards the interplay between these factors being crucial for the regulation of cellular metabolism and survival in times of oxygen stress, which has particular relevance for tumour formation. Mdm2, p53 and HIF1α all respond to hypoxia, and intriguingly, have distinct roles depending on the level of hypoxia. The data from numerous studies across different conditions hint at the interplay between these key factors in cellular homeostasis. Here we try to weave these strands together, to create a picture of the complex tapestry of interactions that demonstrates the importance of the crosstalk between these key regulatory proteins during hypoxia.