DNp73a is an isoform of the p53 homologue p73 that lacks an amino-terminal transactivation domain and antagonizes the induction of gene expression by p53. Here, we examined whether DNp73a might also modulate cellular transcription in the absence of p53. The expression of DNp73a in the p53À/À cell line H1299 reduced the mRNA levels of p21/CDKN1A, but did not affect other p53-responsive genes. Correspondingly, the p21/ CDKN1A promoter was downregulated by DNp73a in reporter assays, whereas other p53-responsive promoters were not inhibited. To identify additional genes that respond to DNp73a in the absence of p53, microarrays carrying 4600 cDNA clones were hybridized. The expression of 30 genes was found to be altered more than threefold by overexpressed DNp73a. For instance, DNp73a increased the expression of EGR1 and CDC6, whereas it decreased the mRNA levels of c-MYC, cyclin A2/CCNA2, NF-jB1, ODC1, and RET finger protein/ RFP. Semiquantitative reverse transcription-PCR confirmed these results and further revealed that the influence of DNp73a on the regulation of these genes differs from other p73 isoforms and p53. We conclude that the impact of DNp73a on gene expression is not limited to p53-responsive genes. Rather, DNp73a can regulate the expression of a variety of genes independently of p53.

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