ΔNp63α promotes apoptosis of human epidermal keratinocytes

Abstract

In this study we show that ΔNp63α overexpression in primary human epidermal keratinocytes causes decreased cell proliferation and increased apoptosis. These changes are associated with increased levels of p21 and p27, decreased cyclin D1 and cyclin E levels, reduced mitochondrial membrane potential, and enhanced procaspase and poly(ADP-ribose) polymerase cleavage. Bcl-xS and Bax levels are increased and Bcl-xL level is reduced. p53 levels are increased in the ΔNp63α-expressing cells and p53 overexpression reproduces features of the ΔNp63α phenotype. Increased p53 expression results in reduced ΔNp63α, suggesting that p53 may negatively regulate ΔNp63α level. ΔNp63α also induces apoptosis in HaCaT and SCC-13 cells, which encode inactive p53 genes, suggesting that the response is p53 independent in these cell lines. Both ΔNp63α and TAp63α reduce SCC-13 cell survival. These studies indicate that both ΔNp63α and TAp63α can negatively regulate keratinocyte survival. © 2007 The Society for Investigative Dermatology.