The p73 gene codes for various different protein isoforms. They include proteins 
expressed under the control of the P1 promoter that contain a transactivation 
domain and are similar in function to p53 (TAp73 isoforms), as well as proteins 
regulated by the P2 promoter that lack this domain and function as dominant 
negative inhibitors of TAp73 and p53 (DeltaNp73 isoforms). Whereas TAp73 
functions as a tumor suppressor with pro-apoptotic function, DeltaNp73 is likely 
to prevent the induction of apoptosis in tumor cells and to participate in 
oncogenesis. Here we used a loss-of-function strategy to assess the role of 
DeltaNp73 in SH-SY5Y neuroblastoma cells. An antisense oligonucleotide designed 
to target DeltaNp73 mRNA, but not TAp73, was used to effectively downregulate 
this transcript. DeltaNp73 downregulation was accompanied by increased levels of 
the pro-apoptotic BH3 family member PUMA at the mRNA and protein level, and by 
conformational activation of BAX which translocated to mitochondria. These 
DeltaNp73 antisense-mediated alterations led to the induction of apoptosis as 
detected by decreased cell viability, augmented DNA fragmentation and increased 
caspase-3 activity in cell lysates. Our results demonstrate the cytoprotective 
role of DeltaNp73 in neuroblastoma and suggest its use as a target for molecular 
intervention therapy.