VHL and neoplasm: The VHL protein, a tumor suppressor and core component of an E3 ubiquitin ligase complex, directly interacts with the oxygen-dependent degradation domain of HIF-1α (amino acids 401 to 603) via residues such as Tyr98, His115, and Ser111 in its β-domain, recruiting E2 enzymes and mediating HIF-1α ubiquitination and proteasomal degradation [50].