Fig. 3
From: Cellular senescence or stemness: hypoxia flips the coin
HIF signaling and effects of hypoxia on stem cells. In normoxia, HIFα proteins can be hydroxilate by PHDs, this allows ubiquitination mediated by VHL and its degradation in proteasome. However, when oxygen levels are low, HIFα proteins are stable, and they can translocate to nucleus where they dimerize with HIF1β and bind to HRE sequences in the DNA. HIF dimers activate transcription of hypoxia response genes. Through this mechanism and others, hypoxia promotes glycolytic flux and expression of stemness-related genes supporting stem cell properties in adult and embryonic stem cells, iPSCs and cancer stem cells. OSKM: Yamanaka factors Oct3/4, Sox2, Klf4 and cMyc