Figure 2. PKM2 contributes to metabolic reprogramming and cancer progression by serving as a PHD3-dependent coactivator for HIF-1.

Prolyl hydroxylation of PKM2 by PHD3 promotes the interaction of PKM2 with HIF-1α, thereby stabilizing HIF-1 binding to the HRE of target genes, recruitment of coactivator p300, histone acetylation, and subsequent transcription of HIF-1 target genes, which encode proteins that are involved in metabolic reprogramming, angiogenesis, and many other critical aspects of cancer progression.