Tazarotene, a member of the new class of acetylenic retinoids, has been shown to 
be effective in the treatment of several hyperproliferative skin diseases, 
including non-melanoma skin cancer. Its effectiveness is thought to rely on the 
ability to activate retinoic acid receptors beta and gamma and to induce a 
number of downstream anti-proliferative genes. Here, we show that the 
p53-related gene p73 is a target of tazarotene. Indeed, tazarotene modulates the 
expression of the p73 gene in immortalized keratinocyte cell lines by inducing 
the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the 
anti-apoptotic and pro-proliferative DeltaNp73 isoforms. This occurs at the 
transcriptional level through a coordinated action on P1p73 and P2p73 promoters 
that control the expression of TA and DeltaN isoforms, respectively. The 
selective downregulation of DeltaNp73 expression by small interfering RNA led to 
an enhancement of tazarotene-induced bax activation and apoptosis, whereas the 
downregulation of both TA and DeltaN isoforms impairs tazarotene-mediated 
apoptosis. These results indicate the relevance of p73 gene products in 
tazarotene-induced growth inhibition and effectiveness in the treatment of skin 
tumors.