FIGURE 1.

Modulation of PHD-HIF1 signaling on neural stem cells (NSCs). Under normoxia, HIF-1α is hydroxylated by PHD at 402 and 564 residues and subsequently recognized and ubiquitinated by the E3 ligase VHL, hereafter, degraded in the proteasome. In response to hypoxia, ROS or PHD inhibitors, the activity of PHD is suppressed and the hydroxylation of HIF-1α by PHD is inhibited. As a result, the stabilized HIF-1α translocates to the nucleus and partners with HIF-1β to form a heterodimer that transcriptionally activates its downstream target genes to promote proliferation or differentiation of NSCs.