Buckbinder L, Talbott R, Seizinger B R, Kley N
Department of Molecular Genetics and Cell Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08540.
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10640-4. doi: 10.1073/pnas.91.22.10640.
The ability of the p53 protein to act as a sequence-specific transcriptional activator suggests that genes induced by p53 may encode critical mediators of p53 tumor suppression. Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance. Wild-type p53-dependent induction of these transcripts was observed in cells that are growth arrested by p53, as well as in cells that undergo apoptosis upon expression of an inducible wild-type p53 transgene. These results show that p53 activates the expression of numerous response genes and suggest that multiple effectors may play a role in mediating cellular functions of p53.
p53蛋白作为序列特异性转录激活因子的能力表明，p53诱导的基因可能编码p53肿瘤抑制的关键介质。利用四环素调控的p53表达系统和cDNA文库消减程序，我们在人Saos-2骨肉瘤细胞中鉴定出几种p53诱导的基因转录本，这些转录本在大小、调控和低丰度方面都是新的。在被p53阻滞生长的细胞以及在诱导型野生型p53转基因表达后发生凋亡的细胞中，观察到了这些转录本的野生型p53依赖性诱导。这些结果表明p53激活了众多反应基因的表达，并提示多种效应因子可能在介导p53的细胞功能中发挥作用。
