Figure 2.

SUMOylation in the hypoxia pathway. SUMOylation plays a positive role in maintaining the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α). SUMO-modified von Hippel–Lindau tumor suppressor (pVHL) cannot modify HIF-1α by ubiquitination and degrade it through proteasomes. Microphthalmia-associated transcription factor (MITF) and chromobox 4 can upregulate HIF-1α and facilitate its nuclear translocation. p300 can be modified by SUMOylation under mildly hypoxic conditions. SUMO-modified p300 can recruit HDAC6 and inhibits the transcriptional activity. This process can be inhibited by SENP3 through deSUMOylating p300 and thus increases the HIF-1-dependent vascular endothelial growth factor (VEGF) expression.