The anti-apoptotic role for p53 following exposure to ultraviolet light does not involve DDB2.
The p53 tumour suppressor is a transcription factor that can either activate or repress the expression of specific genes in response to cellular stresses such as exposure to ultraviolet light. The p53 protein can exert both pro- and anti-apoptotic effects depending on cellular context. In primary human fibroblasts, p53 protects cells from UV-induced apoptosis at moderate doses but this is greatly affected by the nucleotide excision repair (NER) capacity of the cells. The damage-specific DNA binding protein 2 (DDB2) is involved in NER and is associated with xeroderma pigmentosum subgroup E (XP-E). Importantly, DDB2 is also positively regulated by the p53 protein. To study the potential interplay between DDB2 and p53 in determining the apoptotic response of primary fibroblasts exposed to UV light, the expression of these proteins was manipulated in primary normal and XP-E fibroblast strains using human papillomavirus E6 protein (HPV-E6), RNA interference and recombinant adenoviruses expressing either p53 or DDB2. Normal and XP-E fibroblast strains were equally sensitive to UV-induced apoptosis over a broad range of doses and disruption of p53 in these strains using HPV-E6 or RNA interference led to a similar increase in apoptosis following exposure to UV light. In contrast, forced expression of p53 or DDB2 did not affect UV-induced apoptosis greatly in these normal or XP-E fibroblast strains. Collectively, these results indicate that p53 is primarily protective against UV-induced apoptosis in primary human fibroblasts and this activity of p53 does not require DDB2.
Cancer Therapeutics Program, Ottawa Health Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
L J
LJ
Stubbert
J M
JM
Smith
J D
JD
Hamill
T L
TL
Arcand
B C
BC
McKay
D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008297:Male; D034622:RNA Interference / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000473:pathology
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D053148:Caspase 3; D053453:Caspase 9