Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nature. 1991 Jul 25;352(6333):345-7. doi: 10.1038/352345a0.
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.
野生型p53蛋白具有许多特性,与其作为肿瘤抑制基因的产物相符。尽管肿瘤抑制基因的正常功能仍大多未知,但似乎它们可能参与促进细胞分化以及介导生长抑制细胞因子引起的生长停滞。因此,许多肿瘤的一个共同特征——野生型p53表达的缺失,可能会消除这些活性。我们现在通过在通常缺乏p53的小鼠髓系白血病细胞系中恢复p53的表达来验证这一观点。使用温度敏感型p53突变体使我们能够分析导入的p53具有野生型或突变特性的细胞。虽然似乎对分化没有影响,但野生型p53的导入导致细胞活力迅速丧失,其方式具有凋亡(程序性细胞死亡)的特征。野生型p53的作用被白细胞介素-6抵消。因此,肿瘤抑制基因的产物可能通过介导凋亡参与限制前体细胞群体。