| First Author | Clarke AR | Year | 1993 |
| Journal | Nature | Volume | 362 |
| Issue | 6423 | Pages | 849-52 |
| PubMed ID | 8479523 | Mgi Jnum | J:60008 |
| Mgi Id | MGI:1352418 | Doi | 10.1038/362849a0 |
| Citation | Clarke AR, et al. (1993) Thymocyte apoptosis induced by p53-dependent and independent pathways [see comments]. Nature 362(6423):849-52 |
| abstractText | Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy. Apoptosis can be initiated by various agents 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 methylpredniso-lone, or etoposide (an inhibitor of topoisomerase II), or after Ca(2+)-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. |
