Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6.
Wild-type p53 protein has many properties consistent with its being the product of a tumour suppressor gene. Although the normal roles of tumour suppressor genes are still largely unknown, it seems that they could be involved in promoting cell differentiation as well as in mediating growth arrest by growth-inhibitory cytokines. Hence, the abrogation of wild-type p53 expression, which is a common feature of many tumours, could eliminate these activities. We have now tested this notion by restoring the expression of p53 in a murine myeloid leukaemic cell line that normally lacks p53. The use of a temperature-sensitive p53 mutant allowed us to analyse cells in which the introduced p53 had either wild-type or mutant properties. Although there seemed to be no effect on differentiation, the introduction of wild-type p53 resulted in rapid loss of cell viability in a way characteristic of apoptosis (programmed cell death). The effect of wild-type p53 was counteracted by interleukin-6. Thus products of tumour suppressor genes could be involved in restricting precursor cell populations by mediating apoptosis.
Yonish-Rouach
E
E
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Resnitzky
D
D
Lotem
J
J
Sachs
L
L
Kimchi
A
A
Oren
M
M
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D016158:Genes, p53; D015850:Interleukin-6 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology*
D015850:Interleukin-6; D016159:Tumor Suppressor Protein p53