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. 2010 Aug 26;6(8):e1001075. doi: 10.1371/journal.ppat.1001075

Figure 8. Model illustrating HIF-1 regulation.

Figure 8

(A) The stability of HIF-1 protein is regulated by oxygen-dependent degradation. The EGL-9 enzyme hydroxylates HIF-1 protein in a reaction that requires molecular oxygen. Once modified, HIF-1 binds VHL-1, which promotes proteasomal degradation of HIF-1. (B) In addition to its role in controlling HIF-1 protein levels, EGL-9 represses HIF-1 transcriptional activity via VHL-1-independent pathway(s). SWAN-1 and RHY-1 also inhibit HIF-1-mediated transcription. MBK-1 acts downstream of SWAN-1 to promote HIF-1 activity. The substrates of the MBK-1 DYRK kinase are not yet known. Combinations of mutations that both stabilize HIF-1 protein and de-repress HIF-1 transcriptional activity cause increased resistance to P. aeruginosa PAO1 fast killing.