el-Deiry W S
Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Semin Cancer Biol. 1998;8(5):345-57. doi: 10.1006/scbi.1998.0097.
The p53 tumor suppressor is the most commonly mutated gene in human cancer. p53 protein is stabilized in response to different checkpoints activated by DNA damage, hypoxia, viral infection, or oncogene activation resulting in diverse biological effects, such as cell cycle arrest, apoptosis, senescence, differentiation, and antiangiogenesis. The stable p53 protein is activated by phosphorylation, dephosphorylation and acetylation yielding a potent sequence-specific DNA-binding transcription factor. The wide range of p53's biological effects can in part be explained by its activation of expression of a number of target genes including p21WAFI, GADD45, 14-3-3 sigma, bax, Fas/APO1, KILLER/DR5, PIG3, Tsp1, IGF-BP3 and others. This review will focus on the transcriptional targets of p53, their regulation by p53, and their relative importance in carrying out the biological effects of p53.
p53肿瘤抑制因子是人类癌症中最常发生突变的基因。p53蛋白在因DNA损伤、缺氧、病毒感染或癌基因激活而激活的不同检查点的响应中得以稳定，从而产生多种生物学效应，如细胞周期停滞、凋亡、衰老、分化和抗血管生成。稳定的p53蛋白通过磷酸化、去磷酸化和乙酰化被激活，产生一种有效的序列特异性DNA结合转录因子。p53广泛的生物学效应部分可由其对许多靶基因表达的激活来解释，这些靶基因包括p21WAFI、GADD45、14-3-3 sigma、bax、Fas/APO1、KILLER/DR5、PIG3、Tsp1、IGF-BP3等。本综述将聚焦于p53的转录靶点、p53对它们的调控以及它们在实现p53生物学效应中的相对重要性。
