DeltaNp63alpha promotes apoptosis of human epidermal keratinocytes.
In this study we show that deltaNp63alpha 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 deltaNp63alpha-expressing cells and p53 overexpression reproduces features of the deltaNp63alpha phenotype. Increased p53 expression results in reduced deltaNp63alpha, suggesting that p53 may negatively regulate deltaNp63alpha level. DeltaNp63alpha 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 deltaNp63alpha and TAp63alpha reduce SCC-13 cell survival. These studies indicate that both deltaNp63alpha and TAp63alpha can negatively regulate keratinocyte survival.
Zhu
Ling
L
Department of Physiology and Biophysics, Case School of Medicine, Cleveland, Ohio, USA.
Rorke
Ellen A
EA
Eckert
Richard L
RL
D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology*; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*; D051020:bcl-X Protein / Q000032:analysis
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein