TP53 and neoplasm: Remarkably, p53 serves as a target for ISGylation and this modification dramatically increased the binding of p53 to the promoter regions of its target genes as well as of its own gene, forming a positive feedback loop, which would amplify the expression of the genes for cell cycle arrest and apoptosis, such as CDKN1 and BAX. Collectively, these results indicate that ISGylation of p53 plays a critical role in cell growth inhibition and thereby in suppression of tumour development under DNA damage conditions.