Letter | Published:

Thymocyte apoptosis induced by p53-dependent and independent pathways

Nature volume 362, pages 849852 (29 April 1993) | Download Citation

Subjects

Abstract

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Int. Rev. exp. Path. 32, 223–254 (1991).

  2. 2.

    , , , & Nature 337, 181–184 (1989).

  3. 3.

    Nature 284, 555–556 (1980).

  4. 4.

    & J. Immun. 139, 3199–3206 (1987).

  5. 5.

    , & Immun, Today 11, 120–121 (1990).

  6. 6.

    , , & Molec. cell. Biol. 13, 711–719 (1993).

  7. 7.

    et al. Nature 352, 345–347 (1991).

  8. 8.

    et al. Proc. natn. Acad. Sci. U.S.A. 89, 4495–4499 (1992).

  9. 9.

    , , , & Nature 326, 292–295 (1987).

  10. 10.

    , & J. Virol. 59, 444–452 (1986).

  11. 11.

    et al. Nature 359, 328–330 (1992).

  12. 12.

    et al. Cancer Res. 51, 1078–1085 (1991).

  13. 13.

    , & Int. J. Rad. Biol. 42, 199–204 (1982).

  14. 14.

    , , , & Cancer Res. 51, 5304–5311 (1991).

  15. 15.

    , , & Proc. natn. Acad. Sci. U.S.A. 89, 7491–7495 (1992).

  16. 16.

    et al. Expl. Cell Res. 200, 416–424 (1992).

  17. 17.

    , & Cancer Res. 51, 6280–6285 (1991).

  18. 18.

    , & Nature 359, 554–556 (1992).

  19. 19.

    , & J. Immun. 147, 4286–4292 (1991).

  20. 20.

    , , & J. Path 142, 67–78 (1984).

  21. 21.

    et al. Cell 71, 587–597 (1992).

  22. 22.

    , , & EMBO J. 3, 2179–2183 (1984).

  23. 23.

    et al. Nucleic Acids Res. 19, 5755–5761 (1991).

  24. 24.

    , , , & Proc. natn. Acad. Sci. U.S.A. 76, 3755–3759 (1979).

  25. 25.

    , , , & Gene 105, 263–267 (1991).

  26. 26.

    , , & Nucleic Acids Res. 11, 6895–6911 (1983).

Download references

Author information

Author notes

    • C. A. Purdie

    Present address: Department of Pathology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK.

Affiliations

  1. Cancer Research Campaign Laboratories, Department of Pathology, University Medical School, Teviot Place, Edinburgh EH8 9AG, UK

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

Authors

  1. Search for A. R. Clarke in:

  2. Search for C. A. Purdie in:

  3. Search for D. J. Harrison in:

  4. Search for R. G. Morris in:

  5. Search for C. C. Bird in:

  6. Search for M. L. Hooper in:

  7. Search for A. H. Wyllie in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/362849a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.