The CUSP ΔNp63α isoform of human p63 is downregulated by solar-simulated ultraviolet radiation

Background: In normal human keratinocytes, a p53-like protein, ΔNp63α, also known as CUSP, is constitutively and abundantly expressed. The significant constitutive expression of ΔNp63α in stratified epithelium has been proposed to maintain the proliferative capacity of basal cells, blocking the consequences of inappropriate p53 activation. Objective: To determine the response of keratinocyte ΔNp63α to ultraviolet radiation (UVR), a stimulus for p53 activation. Methods: Cultured normal human keratinocytes were exposed to graded doses of solar-simulated UVR. The expression of ΔNp63α protein and mRNA were measured with Western and Northern blotting. Normal mouse skin was exposed to UVR, and ΔNp63α expression assessed with immunohistochemistry. Results: Increasing doses of UVR virtually shut off ΔNp63α protein and mRNA expression in cultured normal human keratinocytes and in normal mouse skin in vivo. Conclusion: This study supports the hypothesis that in situations where p53 activation is desirable, as with DNA-damaging UVR, ΔNp63α downregulation occurs and may possibly allow for better target gene transcription by p53.