Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Wednesday 23 August 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Letters to Nature
Nature 362, 849 - 852 (29 April 1993); doi:10.1038/362849a0

Thymocyte apoptosis induced by p53-dependent and independent pathways

A. R. Clarke, C. A. Purdie*, D. J. Harrison, R. G. Morris, C. C. Bird, M. L. Hooper & A. H. Wyllie

Cancer Research Campaign Laboratories, Department of Pathology, University Medical School, Teviot Place, Edinburgh EH8 9AG, UK
*Present address: Department of Pathology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK.

DEATH by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy1. Apoptosis can be initiated by various agents1–5 and may be a result of expression of the oncosuppressor gene p53 (refs 6–8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca2+-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.

------------------

References

1. Arends, M. J. & Wyllie, A. H. Int. Rev. exp. Path. 32, 223−254 (1991). | PubMed | ChemPort |
2. Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181−184 (1989). | Article | PubMed | ISI | ChemPort |
3. Wyllie, A. H. Nature 284, 555−556 (1980). | Article | PubMed | ISI | ChemPort |
4. Sellins, K. S. & Cohen, J. J. J. Immun. 139, 3199−3206 (1987). | PubMed | ChemPort |
5. McConkey, D. J., Orrenius, S. & Jondal, M. Immun, Today 11, 120−121 (1990). | ChemPort |
6. Ryan, J. J., Danish, R., Gottlieb, C. A. & Clarke, M. F. Molec. cell. Biol. 13, 711−719 (1993). | PubMed | ChemPort |
7. Yonish-Rouach, E. et al. Nature 352, 345−347 (1991). | Article | PubMed | ChemPort |
8. Shaw, P. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4495−4499 (1992). | ChemPort |
9. Hooper, M. L., Hardy, K., Handyside, A., Hunter, S. & Monk, M. Nature 326, 292−295 (1987). | Article | PubMed | ISI | ChemPort |
10. Yewdell, J. W., Gannon, J. V. & Lane, D. P. J. Virol. 59, 444−452 (1986). | PubMed | ChemPort |
11. Clarke, A. R. et al. Nature 359, 328−330 (1992). | Article | PubMed | ISI | ChemPort |
12. Walker, P. R. et al. Cancer Res. 51, 1078−1085 (1991). | PubMed | ChemPort |
13. Zhivotovsky, B. D., Seiliev, A. A. & Hanson, K. P. Int. J. Rad. Biol. 42, 199−204 (1982). | ChemPort |
14. Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B. & Craig, R. W. Cancer Res. 51, 5304−5311 (1991). | PubMed |
15. Kuerbitz, S. J., Plunkett, B. S., Walsh, M. V. & Kastan, M. B. Proc. natn. Acad. Sci. U.S.A. 89, 7491−7495 (1992). | ChemPort |
16. Roy, C. et al. Expl. Cell Res. 200, 416−424 (1992). | ChemPort |
17. Bertrand, R. Sarang, M. Jenkin, J., Kerrigan, D. & Pommier, Y. Cancer Res. 51, 6280−6285 (1991). | PubMed | ISI | ChemPort |
18. Fanidi, A., Harrington, E. A. & Evan, G. I. Nature 359, 554−556 (1992). | Article | PubMed | ISI | ChemPort |
19. Iseki, R., Mukai, M. & Iwata, M. J. Immun. 147, 4286−4292 (1991). | PubMed | ChemPort |
20. Wyllie, A. H., Morris, R. G., Smith, A. L. & Dunlop, D. J. J. Path 142, 67−78 (1984). | PubMed | ChemPort |
21. Kastan, M. B. et al. Cell 71, 587−597 (1992). | Article | PubMed | ISI | ChemPort |
22. Bienz, B., Zakut-Houri, R., Givol, D. & Oren, M. EMBO J. 3, 2179−2183 (1984). | PubMed | ISI | ChemPort |
23. McBurney, M. W. et al. Nucleic Acids Res. 19, 5755−5761 (1991). | PubMed | ISI | ChemPort |
24. Colbere-Garapin, F., Chousterman, S., Horodniceanu, F., Kourilisky, P. & Garapin, A.-X. Proc. natn. Acad. Sci. U.S.A. 76, 3755−3759 (1979). | ChemPort |
25. van der Lugt, N., Robanus Maandag, E., te Riele, H., Laird, P. W. & Berns, A. Gene 105, 263−267 (1991). | PubMed | ChemPort |
26. Kaster, K. R., Burgett, S. G., Rao, R. N. & Ignolia, T. D. Nucleic Acids Res. 11, 6895−6911 (1983). | PubMed | ChemPort |



© 1993 Nature Publishing Group
Privacy Policy