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


CONCLUSIONS
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.
Marchbank
Angela
A
Department of Dermatology, University of Colorado School of Medicine, Denver, CO, USA.
Su
Lih-Jen
LJ
Walsh
Patrick
P
DeGregori
James
J
Penheiter
Kristi
K
Grayson
Timothy B E
TB
Dellavalle
Robert P
RP
Lee
Lela A
LA
D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013472:Sunlight; D013997:Time Factors; D015534:Trans-Activators; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C077214:L1Hs-encoded protein p40, human