Several pathways that lead to increased turnover of all PML isoforms in tumour cells have been revealed [27], including ubiquitination by E6AP, an E3 ligase that is targeted in HPV-positive cervical carcinomas [54], and a hypoxia-induced mechanism mediated by KLHL20 [55]; proteasome inhibitor treatment promoted PML re-expression and restoration of PML-NBs in several PML negative tumor cell lines [28]. This evidence concerns the gene UBE3A and neoplasm.