For instance, upon transcriptional activation through HIF1α, circPFKFB4 binds to damage specific DNA binding protein 1 (DDB1)/DDB2 and aids in cullin-ring ligase-4 (CRL4)-DDB2 ubiquitin ligase assembly, which in turn promotes cancer cell proliferation by specifically increasing the degradation of tumor suppressor p27 (74). Here, DDB2 is linked to cancer.