Regulation of p53 in response to ionizing radiation in ataxia telangiectasia fibroblasts.
OBJECTIVE
An analysis of the structure and expression of p53 in fibroblasts from patients with ataxia telangiectasia (AT) is presented.


METHODS
p53 status in primary and SV40 T antigen-transformed AT cell lines was analyzed using immunocytochemistry and by sequencing with the dideoxynucleotide termination method. The expression of p53 transcript was measured by Northern analysis. The kinetics of p53 protein expression and DNA-binding activity were measured at various intervals following irradiation.


RESULTS
No mutation of p53 sequences was found in AT cells. Decreased levels of p53 mRNA and protein were observed in AT5BIVA cells compared to other SV40 T antigen-immortalized fibroblasts. Furthermore, DNA-protein binding analysis shows that a fraction of p53 in the nuclear extracts from AT5BIVA is regulated and binds to specific DNA sequence following irradiation.


CONCLUSIONS
These data provide evidence for a heterogeneity of the p53 function in SV40-transformed AT cells. It also supports the hypothesis that a regulatory mechanism of p53 activity remains in T antigen-expressing cells in response to ionizing radiation damage.
Jung
M
M
Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Lee
S A
SA
Zhang
Y
Y
Dritschilo
A
A
D001260:Ataxia Telangiectasia / Q000235:genetics*; D002461:Cell Line, Transformed / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000528:radiation effects*; D016158:Genes, p53 / Q000528:radiation effects*; D006801:Humans; D017422:Sequence Analysis, DNA; D013539:Simian virus 40; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*
D016159:Tumor Suppressor Protein p53; D004247:DNA