Dual regulation of the ΔNp63 transcriptional activity by ΔNp63 in human nasopharyngeal carcinoma cell

p63 splicing variants lacking NH2-terminal transactivating domain, known as ΔNp63, are thought to antagonize p53 and p63 functions and are suggested to play roles in keratinocyte differentiation. Here, we show that ΔNp63 has a dual-regulatory effect on the activity of its own promoter in NPC-076 cell. Down-regulation of the transcriptional activity is observed when ΔNp63 is present in low levels. In contrast, up-regulation of ΔNp63 transcriptional activity is observed when ΔNp63 is expressed at higher levels. The down-regulation effect is abolished when the p53-binding site of the ΔNp63 promoter is mutated. In sharp contrast, similar mutation does not affect the up-regulation of the ΔNp63 transcriptional activity under the same experimental conditions. Further study shows that the up-regulation is correlated with the activation of the STAT3, as the blockade of STAT3 nuclear translocation abolishes the up-regulation by ΔNp63. Thus, ΔNp63 exerts a bidirectional regulation of the ΔNp63 transcriptional activity in NPC-076 cell.