p53 involvement in control of G2 exit of the cell cycle: role in DNA damage-induced apoptosis.
p53 involvement in control of G2 exit of the cell cycle: role in DNA damage-induced apoptosis.
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发表时间：
1995-06
期刊：
影响因子：
8
通讯作者：
C. Guillouf;Filippo Rosselli;K. Krishnaraju;E. Moustacchi;B. Hoffman;D. Liebermann
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文献类型：
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作者：
C. Guillouf;Filippo Rosselli;K. Krishnaraju;E. Moustacchi;B. Hoffman;D. Liebermann
增殖的哺乳动物细胞中的 DNA 损伤会诱导复杂的细胞反应，包括细胞周期的扰动和程序性细胞死亡。使用 p53 表达无效的 M1 成髓细胞白血病细胞、表达 p53ts 和 bcl-2 转基因的基因工程 M1 变体，以及从野生型 p53 (wt p53) 和p53 缺陷小鼠。结果表明，M1p53ts 细胞的伽马射线照射激活了温度敏感突变体转基因 p53 (p53ts) 的功能，相对于亲本、无效 p53 M1 细胞，促进细胞凋亡增加。还表明，对于上述所有不同的造血细胞类型，伽马射线照射诱导的凋亡细胞死亡的动力学与退出伽马射线诱导的 G2 停滞的速度相关。最后，获得的数据表明，除了在细胞凋亡和 G1 停滞中发挥作用外，野生型 p53 还正向调节伽马射线诱导的 G2 检查点的退出。总而言之，这些发现表明 p53 的这一新功能是 p53 在细胞凋亡中发挥其作用的生理途径的一个组成部分。
DNA damage in proliferating mammalian cells induces a complex cellular response comprising perturbation of the cell cycle and programmed cell death. The relationship between p53-dependent and p53-independent apoptotic cell death, as well as the cell cycle checkpoints induced by DNA damaging agents were explored in hematopoietic cells, using M1 myeloblastic leukemia cells, which are null for p53 expression, genetically engineered M1 variants, expressing p53ts and bcl-2 transgenes, as well as myeloblast enriched bone-marrow cells obtained from wild type p53 (wt p53) and p53-deficient mice. It is shown that gamma-irradiation of M1p53ts cells activated a function of the temperature sensitive mutant transgene p53 (p53ts), promoting increased apoptosis relative to parental, null p53 M1 cells. It is also shown that the kinetics of apoptotic cell death induced by gamma-irradiation correlated with the rapidity of exit from gamma-ray-induced G2 arrest for all the different hematopoietic cell types indicated above. Finally, data has been obtained to demonstrate that, in addition to a role in apoptosis and G1 arrest, wild-type p53 positively modulated the exit from the gamma-ray-induced G2 checkpoint. Taken together, these findings indicate that this new function for p53 is a component of the physiological pathway by which p53 exerts its role in apoptosis.