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Role for c-Abl and p73 in the radiation response of male germ cells

Oncogene volume 20, pages 4298–4304 (2001)Cite this article

Abstract

p53 plays a central role in the induction of apoptosis of spermatogonia in response to ionizing radiation. In p53−/− testes, however, spermatogonial apoptosis still can be induced by ionizing radiation, so p53 independent apoptotic pathways must exist in spermatogonia. Here we show that the p53 homologues p63 and p73 are present in the testis and that p73, but not p63, is localized in the cytoplasm of spermatogonia. Unlike p53, neither p63 nor p73 protein levels were found to increase after a dose of 4 Gy of X-rays. Although p73 protein levels did not increase, its interaction with the non-receptor tyrosine kinase c-Abl and its phosphorylation on tyrosine residues did. c-Abl and p73 co-localize in the cytoplasm of spermatogonia and spermatocytes and in the residual bodies. Furthermore, c-Abl protein levels increase after irradiation. p63 was not found to co-localize or interact with c-Abl neither before nor after irradiation. In conclusion, in the testis ionizing radiation elevates cytoplasmic c-Abl that in turn interacts with p73. This may represent an additional, cytoplasmic, apoptotic pathway. Although less efficient than the p53 route, this pathway may cause spermatogonial apoptosis as observed in p53 deficient mice.

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Acknowledgements

The authors thank René MC Scriwanek and Marc A van Peski for assistance with photography and Ans MM van Pelt for advice and discussions. This work was supported by the JA Cohen Institute for Radiopathology and Radiation Protection, Leiden, The Netherlands.

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Authors and Affiliations

  1. Department of Cell Biology, UMCU, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands

    Geert Hamer & Dirk G de Rooij

  2. Department of Radiotherapy, UMCU, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands

    Iris S Gademan & Henk B Kal

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  1. Geert Hamer
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  2. Iris S Gademan
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Correspondence to Geert Hamer.

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Hamer, G., Gademan, I., Kal, H. et al. Role for c-Abl and p73 in the radiation response of male germ cells. Oncogene 20, 4298–4304 (2001). https://doi.org/10.1038/sj.onc.1204568

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