When p53 needs p73 to be functional – forced p73 expression induces nuclear accumulation of endogenous p53 protein

In human neuroblastoma (NB), wild type p53 protein does not elicit its archetypal human tumor suppressive activity so far described. To elucidate this alteration, substantial investigations using NB cell lines have underscored p53 protein nuclear localization defect and/or inappropriate conformation, but no definitive evidence has been provided so far. p73, the first homologue of the p53 gene, locates at the 1p36.3 locus, which is known to be deleted in various human tumors including NB. Unlike p53 mRNA, which specifies a single protein, p73alpha mRNAs encode two types of isoform (TAp73α and ΔNp73α) resulting from the use of two different promoters, and eliciting or lacking NH2-terminal transactivation domain, respectively. ΔNp73α inhibits p53 pro-apoptotic function in murine developing neurons and is abundantly expressed in human undifferentiated NB tumors. However, critical issues have been raised regarding p73α isoform roles, and their possible link to p53 are yet to be clarified in human NB using adenoviral infection approach.