MDM2 and neoplasm: Tumours may possess wild type p53, but it may not be fully active and its response to stress may be dampened by alterations in other factors such as amplification of the p53 ubiquitin E3 ligase HDM2, loss of p14ARF tumour suppressor or the expression of oncoviral proteins that inhibit p53 and target it for degradation (Kensuke and Vassilev, 2015).