Wolkowicz R, Rotter V
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Pathol Biol (Paris). 1997 Dec;45(10):785-96.
The p53 tumor suppressor gene is a critical regulator of normal development involved in cell cycle control pathways, such as growth arrest, differentiation and apoptosis. The DNA binding activity of p53 is central to its function. In addition to the specific DNA binding activity that is confined to the "core" domain of the molecule, the C-terminus seems to play an important role in both controlling the specific as well as exhibiting a non-specific DNA binding activity, which is directly associated with sensing damaged DNA. The C-terminal DNA binding activity appears to be regulated by phosphorylation, glycosylation, splicing and binding of several factors. The C-terminus seems to recognize single and double stranded DNA breaks that occur during DNA replication and recombination, as well as following external DNA stress signals. Unless the cell manages to correct the DNA damage it has the tempting option to progress towards apoptosis. Imagine the C-terminus as a traffic light ensuring the safe "on going" through the cell cycle; in case damaged DNA could not be corrected, p53 dependent apoptosis or terminal differentiation "signs" are turned on!
p53肿瘤抑制基因是正常发育的关键调节因子，参与细胞周期控制途径，如生长停滞、分化和凋亡。p53的DNA结合活性是其功能的核心。除了局限于分子“核心”结构域的特异性DNA结合活性外，C末端似乎在控制特异性以及表现出非特异性DNA结合活性方面都起着重要作用，这种非特异性DNA结合活性与感知受损DNA直接相关。C末端的DNA结合活性似乎受磷酸化、糖基化、剪接和几种因子结合的调节。C末端似乎能识别DNA复制和重组过程中以及外部DNA应激信号后出现的单链和双链DNA断裂。除非细胞设法修复DNA损伤，否则它就会倾向于走向凋亡。可以将C末端想象成一个交通信号灯，确保细胞周期安全“通行”；如果受损DNA无法修复，依赖p53的凋亡或终末分化“信号”就会开启！
