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DNA Damage Increases the Levels of MDM2 Messenger RNA in wtp53 Human Cells¹

Stress Protein Group, Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts 02115

² To whom requests for reprints should be addressed, at Joint Center for Radiation Therapy, 50 Binney St., Boston, MA 02115.

Damage to chromosomal DNA increases the levels of the transcriptional regulatory protein p53. We have investigated how the MDM2 protein, which binds to p53 and inactivates its transcriptional activity, may be controlled following DNA damage. Irradiation of human GM2149 fibroblast cells causes an increase in MDM2 mRNA levels within 1 h, and levels remain elevated for at least 8 h. The induction of MDM2 mRNA following irradiation is not blocked by inhibitors of protein synthesis and can be detected after doses of 2-5 Gy. In ataxia telangiectasia cells or cells where p53 is mutated/deleted, MDM2 mRNA levels are not increased after DNA damage. This suggests that p53 is required for transcription of the MDM2 gene following DNA damage.

¹ Supported by funds from the Joint Center for Radiation Therapy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 11/17/93. Accepted 1/ 5/94.

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