p73 is a p53-related transcription factor with fundamental roles in development 
and tumor suppression. Transcription from two different promoters on the p73 
gene results in generation of transcriptionally active TAp73 isoforms and 
dominant negative DeltaNp73 isoforms with opposing pro- and anti-apoptotic 
functions. Therefore, the relative ratio of each isoform is an important 
determinant of the cell fate. Proteasomal degradation of p73 is mediated by 
polyubiquitination-dependent and -independent processes both of which appear, 
thus far, to lack selectivity for the TAp73 and DeltaNp73 isoforms. Here, we 
describe the characterization of another transcriptional target of TAp73; a ring 
finger domain ubiquitin ligase p73 Induced RING 2 protein (PIR2). Although PIR2 
was initially identified a p53-induced gene (p53RFP), low abundance of PIR2 
transcript in mouse embryonic fibroblasts of TAp73 KO mice compared with WT mice 
and comparison of PIR2 mRNA and protein levels following TAp73 or p53 
overexpression substantiate TAp73 isoforms as strong inducers of PIR2. Although 
PIR2 expression was induced by DNA damage, its expression did not alter 
apoptotic response or cell cycle profile per se. However, coexpression of PIR2 
with TAp73 or DeltaNp73 resulted in an increase of the TA/DeltaNp73 ratio, due 
to preferential degradation of DeltaNp73. Finally, PIR2 was able to relieve the 
inhibitory effect of DeltaNp73 on TAp73 induced apoptosis following DNA damage. 
These results suggest that PIR2, by being induced by TAp73 and degrading 
DeltaNp73, differentially regulates TAp73/DeltaNp73 stability, and, hence, it 
may offer a therapeutic approach to enhance the chemosensitivity of tumor cells.