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Radiation with 1 Gy Prevents the Activation of the Mitotic Inducers Mitosis-promoting Factor (MPF) and cdc25-C in HeLa Cells¹

Department of Pathochemistry (0210), German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg [H. B., V. K.], and Cell Biology Program, European Molecular Biology Laboratory, Postfach 102209, D-69012 Heidelberg [I. H.], Germany

The mechanism of the transient G₂ arrest induced by small doses of ionizing radiation involves the failure to activate the correctly formed pre-mitosis-promoting factor (MPF) complex of cyclin B and p34^cdc2 by dephosphorylation at Tyr15 of the latter, as recent studies of other laboratories have indicated. Similar data were obtained with the G₂ arrest-inducing agents epidermal growth factor and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (H. Barth and V. Kinzel, Exp. Cell Res., 212: 383–388, 1994, and H. Barth and V. Kinzel, J. Cell. Physiol., 162: 44–51, 1995). To differentiate the radiation consequences in synchronized HeLa cells from those of 12-O-tetradecanoylphorbol-13-acetate and epidermal growth factor, experiments with a very small dose (1 Gy) have been carried out in cells close to the G₂-M border and, for comparison, in mitotic cells. We show that in addition to the failure of p34^cdc2 dephosphorylation at Tyr15, radiation with 1 Gy also prevents the activation of the phosphatase cdc25-C, the enzyme catalyzing the MPF activation. In contrast, irradiation of mitotic cells with 1 Gy did not influence that fraction of either MPF or cdc25-C already activated. Moreover, the gain in MPM-2 antigenicity of cdc25-C, usually indicative of an activating phosphorylation, is shown to be prevented by 1 Gy. The data indicate that the initiation of the proposed autocatalytic loop between MPF and cdc25-C becomes interrupted by radiation, but they give no hint at which point.

¹ Work supported by the Deutsche Forschungsgemeinschaft.

² To whom requests for reprints should be addressed. Phone: +49-6221-423253; Fax: +49-6221-423259.

Received 1/18/96. Accepted 3/26/96.

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