1. ¹Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, 122 Diggs Bldg, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA;
2. ²Center for Genomics Research, Boonshoft School of Medicine, Wright State University, 3640 Col Glenn Highway, Dayton, OH 45435, USA

Correspondence: Madhavi Kadakia, Tel: +1-937-775-2339; Fax: +1-937-775-3730 E-mail: madhavi.kadakia@wright.edu

^*These authors contributed equally to this work

Received 21 April 2008; Revised 22 May 2008; Accepted 26 May 2008.

Abstract

p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicing of the p63 gene gives rise to p63 isoforms, which can act either as tumor suppressors or as oncogene. In this report, we studied the effects of naturally occurring TAp63 mutants on the regulation of p53/p63 and p63 specific target genes. We observed significant differences among p63 mutants to regulate the p53/p63 and p63 specific target genes. Additionally, we observed a differential effect of p63 mutants on wildtype-p63-mediated induction of p53/p63 and p63 specific target genes. We also demonstrated that these mutants differentially regulate the binding of wildtype p63 to the promoter of target genes. Furthermore, the effects of these mutants on cell death and survival were consistent with their ability to regulate the downstream targets when compared to wildtype TAp63. In summary, our data demonstrate that p63 mutants exhibit differential effects on p63 and p53/p63 specific target genes and on the induction of apoptosis, and provide further insight into the function of p63.