Fig. 5.

Molecular signals affecting HIF-1α regulation. Induction of Ras, PI3K, and AKT phosphorylation mediated by RTK activation or integrin ligation leads to increased HIF-1α by modulating its stability and increased translation by the PI3K/AKT/mTOR pathway. TP53 negatively modulates this process by inducing MDM2, which can ubiquitinate and lead to HIF-1α degradation by the proteasome pathway.