Yonish-Rouach E, Grunwald D, Wilder S, Kimchi A, May E, Lawrence J J, May P, Oren M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Mol Cell Biol. 1993 Mar;13(3):1415-23. doi: 10.1128/mcb.13.3.1415-1423.1993.
M1 clone S6 myeloid leukemic cells do not express detectable p53 protein. When stably transfected with a temperature-sensitive mutant of p53, these cells undergo rapid cell death upon induction of wild-type (wt) p53 activity at the permissive temperature. This process has features of apoptosis. In a number of other cell systems, wt p53 activation has been shown to induce a growth arrest. Yet, wt 53 fails to induce a measurable growth arrest in M1 cells, and cell cycle progression proceeds while viability is being lost. There exists, however, a relationship between the cell cycle and p53-mediated death, and cells in G1 appear to be preferentially susceptible to the death-inducing activity of wt p53. In addition, p53-mediated M1 cell death can be inhibited by interleukin-6. The effect of the cytokine is specific to p53-mediated death, since apoptosis elicited by serum deprivation is refractory to interleukin-6. Our data imply that p53-mediated cell death is not dependent on the induction of a growth arrest but rather may result from mutually incompatible growth-regulatory signals.
M1克隆S6髓系白血病细胞不表达可检测到的p53蛋白。当用p53的温度敏感突变体进行稳定转染时，这些细胞在允许温度下诱导野生型（wt）p53活性后会迅速发生细胞死亡。这个过程具有凋亡的特征。在许多其他细胞系统中，野生型p53激活已被证明可诱导生长停滞。然而，野生型p53未能在M1细胞中诱导可测量的生长停滞，并且在细胞活力丧失的同时细胞周期仍在进行。然而，细胞周期与p53介导的死亡之间存在关联，G1期的细胞似乎对野生型p53的死亡诱导活性更为敏感。此外，p53介导的M1细胞死亡可被白细胞介素-6抑制。细胞因子的作用对p53介导的死亡具有特异性，因为血清剥夺引发的凋亡对白细胞介素-6不敏感。我们的数据表明，p53介导的细胞死亡不依赖于生长停滞的诱导，而可能是由相互不兼容的生长调节信号导致的。
