Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factors 1 alpha

Tumor angiogenesis and its regulation by p53-induced degradation of hypoxia-inducible factors 1 alpha are discussed. It has been shown that homozygous deletion of the p53 tumor suppressor gene using homologous recombination in a human cancer cell line promotes neovascularization and growth of tumor xenografts in nude mice. That p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1 alpha subunit of hypoxia inducible factor 1 (HIF-1). HIF-1 is a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis responding to insufficient oxygen. Amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.