Ewen M E, Miller S J
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biochim Biophys Acta. 1996 Mar 18;1242(3):181-4. doi: 10.1016/0304-419x(95)00010-d.
The tumor suppressor p53 plays a role in mediating a G1 arrest (for example, in response to DNA damage), in the cellular commitment to apoptosis and in suppression of transformation. The mechanism of action of p53 in each of these biological outcomes is likely to be overlapping. Current data indicate that p53 functions as a sequence specific transcriptional activator. p53 can also repress transcription from certain promoters. One way in which p53 mediates a G1 arrest after DNA damage appears to be clear. Cells exposed to ionizing radiation show elevated levels of p53 protein. The increase in p53 levels is thought to be responsible for the increase in the cyclin-dependent kinase (cdk) inhibitor p21 mediated through the p53 binding sites in the p21 promoter. With regard to the ability of p53 to suppress transformation, there is data suggesting that p53 functions other than, or in addition to, its transcriptional activation function may be necessary. Similar data exist for p53-dependent apoptosis. Recently a role for p53 at another level of gene regulation, namely, translational regulation has been proposed. p53 associates with various components of the translation machinery and has been implicated in the translational regulation of both the p53 and CDK4 mRNAs. Here we will summarize the evidence suggesting a role for p53 in translation and how this regulation might be achieved.
肿瘤抑制因子p53在介导G1期阻滞（例如，对DNA损伤的反应）、细胞凋亡的发生以及抑制细胞转化过程中发挥作用。p53在这些生物学效应中的作用机制可能相互重叠。目前的数据表明，p53作为一种序列特异性转录激活因子发挥作用。p53也可以抑制某些启动子的转录。p53在DNA损伤后介导G1期阻滞的一种方式似乎很明确。暴露于电离辐射的细胞显示p53蛋白水平升高。p53水平的升高被认为是通过p21启动子中的p53结合位点介导的细胞周期蛋白依赖性激酶（cdk）抑制剂p21增加的原因。关于p53抑制细胞转化的能力，有数据表明，p53除了其转录激活功能之外，或在此功能之外，其其他功能可能也是必需的。p53依赖性细胞凋亡也存在类似的数据。最近，有人提出p53在基因调控的另一个层面，即翻译调控中发挥作用。p53与翻译机制的各种成分相关联，并参与了p53和CDK4 mRNA的翻译调控。在这里，我们将总结表明p53在翻译中发挥作用的证据以及这种调控可能是如何实现的。
