VHL and neoplasm: pVHL binds to elongin C and CUL2, thus forming the VCB–CUL2 complex with elongin B. Under normal oxygen conditions, acetylation and hydroxylation of proline residues in the oxygen-dependent degradation domain (ODD) of HIF-α induces binding to the VCB–CUL2 complex and functions as an anti-tumor when HIF-1α is degraded via the ubiquitin–proteasome pathway [19].