While HIF 1-alpha is rapidly upregulated by SerpinB3 at the transcriptional level, promoting cell survival and angiogenesis, HIF 2-alpha is stabilized by SerpinB3 that prevents its proteasomal degradation, via selective NEDDylation, promoting cell proliferation and favouring HCC progression in a positive loop with SerpinB3 induction [148]. The gene discussed is EPAS1; the disease is hepatocellular carcinoma.