Jayaraman J, Prives C
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Cell. 1995 Jun 30;81(7):1021-9. doi: 10.1016/s0092-8674(05)80007-8.
Upon cellular DNA damage, the p53 tumor suppressor protein transmits a signal to genes that control the cell cycle and apoptosis. One function of p53 that is important for its role in this pathway is its ability to function as a sequence-specific transcriptional activator. We demonstrate here that short single DNA strands can markedly stimulate the ability of human and murine p53 proteins to bind specifically to a p53 response element in supercoiled DNA. We also show that single-stranded DNA does not stimulate binding by a truncated p53 that lacks the C-terminal domain. Finally, we establish that a peptide spanning the p53 C-terminus has the ability in trans to stimulate sequence-specific DNA binding by p53 dramatically. These data taken together suggest a model in which the p53 C-terminus can recognize DNA structures resulting from damage-induced lesions, and this interaction can be propagated to regulate positively p53 sequence-specific DNA binding.
在细胞DNA受损时，p53肿瘤抑制蛋白会向控制细胞周期和细胞凋亡的基因传递信号。p53在该信号通路中发挥作用的一个重要功能是其作为序列特异性转录激活因子的能力。我们在此证明，短单链DNA能显著刺激人和小鼠p53蛋白与超螺旋DNA中p53反应元件特异性结合的能力。我们还表明，单链DNA不会刺激缺乏C末端结构域的截短型p53的结合。最后，我们证实，一段跨越p53 C末端的肽能够反式显著刺激p53的序列特异性DNA结合。综合这些数据表明了一种模型，即p53 C末端能够识别由损伤诱导的损伤产生的DNA结构，并且这种相互作用能够传递以正向调节p53的序列特异性DNA结合。
