Signaling to p53

作者：Carol Prives · 发表于：Cell · 年份：1998 · DOI：10.1016/s0092-8674(00)81774-2 · 被引用次数：630 · 研究领域：Cancer-related Molecular Pathways、Epigenetics and DNA Methylation、Ubiquitin and proteasome pathways

The p53 tumor suppressor protein transmits signals arising from various forms of cellular stress, including DNA damage, hypoxia, and nucleotide deprivation, to genes and factors that induce cell cycle arrest and cell death. We can thus define events as being upstream or downstream of p53. The endpoint of the upstream component of this pathway is that levels of the p53 protein are dramatically increased through posttranscriptional mechanisms, often by one or two orders of magnitude. There is also evidence that in addition to elevating p53 levels, such signals convert the protein from an inert form to one that is activated for sequence-specific transcriptional activation (reviewed in Ko and Prives 1996). Stress signals are not the only means by which p53 becomes stabilized. The DNA viruses SV40 and adenovirus encode gene products, T antigen and E1a, respectively, that lead to increased quantities of p53 protein in cells. Moreover, under some conditions expression of cellular factors such as Myc or Ras can also result in p53 induction. Although this might seem at odds with the outcome of transformation caused by viral or cellular oncogenes, viruses and cells have evolved several ways to counteract the growth suppression functions of induced p53. The downstream component of the p53 pathway has been relatively well explored, and many transcriptional targets of p53 have been identified and characterized, including the gene encoding the CDK inhibitor, p21. By contrast, the upstream ...