Other studies [110] suggest that Cbx4 (a member of the polycomb group and a previously characterized SUMO E3 ligase) is responsible for the sumoylation of HIF-1α under hypoxia and in contrast to PIASy, Cbx4 was shown to increase HIF-1 activity and, subsequently, hypoxia-induced VEGF expression and angiogenesis in HCC cells and transplanted mice HCC models. The gene discussed is CBX4; the disease is hepatocellular carcinoma.