Identification and tissue distribution of novel KET/p63 splice variants

The human p53 protein family comprises three members - p53, p63 and p73. Whereas only one p53 variant is known multiple isoforms of p63 and p73 have been described. Depending on the isoform p63 influences p53-responsive genes in a p53-like or -distinct manner. We have cloned multiple splice variants of keratinocyte transcription factor (KET), the rat ortholog of human p63. Several tissue specific variations of exon 1 resulting in different amino-terminal ends were identified. Transactivation properties of the splice variants inversely correlated with the length of the N-termini as determined by activation of the p53-responsive p21 promotor. Multiple KET isoforms are colocalized in different rat tissues. The amino-terminal truncated form DeltaNKETalpha is expressed in epithelial tissues, while expression of the most p53-like KET isotype TAKETgamma was detected in skeletal muscle. Expression of a major KET variant appears to be a cell-type specific rather than a differentiation specific phenomenon.