The CUSP DeltaNp63alpha isoform of human p63 is downregulated by solar-simulated ultraviolet radiation.

Marchbank A, Su LJ, Walsh P, DeGregori J, Penheiter K, Grayson TB, Dellavalle RP, Lee LA.

Journal of dermatological science · 2003

Read the original publication at the publisher’s page

Abstract

Background In normal human keratinocytes, a p53-like protein, DeltaNp63alpha, also known as CUSP, is constitutively and abundantly expressed. The significant constitutive expression of DeltaNp63alpha 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 DeltaNp63alpha 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 DeltaNp63alpha protein and mRNA were measured with Western and Northern blotting. Normal mouse skin was exposed to UVR, and DeltaNp63alpha expression assessed with immunohistochemistry. Results Increasing doses of UVR virtually shut off DeltaNp63alpha 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, DeltaNp63alpha downregulation occurs and may possibly allow for better target gene transcription by p53.