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p53-dependent p21 Induction following -Irradiation without Concomitant p53 Induction in a Human Peripheral Neuroepithelioma Cell Line¹

Department of Biochemistry and Biophysics and the University of North Carolina-Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 [J. S. I., B. E. W.], and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [C. C., B. A. M., J. K. S., J. C. B.]

We previously generated cell hybrids between a derivative of the E6-containing HeLa cell line and a p53 null peripheral neuroepithelioma (PNET) cell line. Although p53 protein from the hybrids was genotypically wild type, it did not demonstrate wild-type behavior. Therefore, in the present study, we introduced wild-type p53 into the PNET parent to investigate whether p53 retained wild-type function within this cell line. Although the p53 null PNET parent lacked detectable p21 protein, introduction of wild-type p53 resulted in a detectable expression of p21 protein in all clones tested, suggestive of wild-type p53 function. In addition, p53 expression was necessary for induction of p21 in response to irradiation, and, furthermore, we show this induction to occur at the transcriptional level. Although introduction of wild-type p53 seems to be responsible for p21 induction, the overall protein levels of p53 were not induced. The involvement of p53 in up-regulating p21 is further substantiated by the observation that p21 up-regulation was dependent on the introduction of the wild-type protein. Our results suggest that wild-type p53 is capable of up-regulating p21 in response to DNA damage in the absence of p53 induction.

¹ Supported in part by NIH Grant CA44470 (to B. E. W.).

² To whom requests for reprints should be addressed, at University of North Carolina-Lineberger Comprehensive Cancer Center, Campus Box 7295, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-7533; Fax: (919) 966-3015.

Received 12/31/96. Accepted 5/13/97.

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