Israeli D, Tessler E, Haupt Y, Elkeles A, Wilder S, Amson R, Telerman A, Oren M
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
EMBO J. 1997 Jul 16;16(14):4384-92. doi: 10.1093/emboj/16.14.4384.
The biological effects of the p53 tumor suppressor protein are elicited, at least in part, through sequence-specific transactivation of a battery of target genes. The differential display method was employed towards identifying additional p53 target genes, with emphasis on genes whose induction may contribute to p53-mediated apoptosis. We report here the cloning of a novel p53-inducible gene, designated PAG608. PAG608 transcripts are induced by DNA damage in a p53-dependent manner. PAG608 encodes a nuclear zinc finger protein, which appears to localize preferentially to nucleoli when expressed at moderate levels in transfected cells. Transient overexpression of PAG608 in human tumor-derived cells leads to distinctive changes in nuclear morphology, and can promote apoptosis. Together with additional p53 target genes, PAG608 may therefore play a role in mediating the biological activities of p53.
p53肿瘤抑制蛋白的生物学效应至少部分是通过一系列靶基因的序列特异性反式激活来引发的。采用差异显示方法来鉴定额外的p53靶基因,重点是那些其诱导可能有助于p53介导的细胞凋亡的基因。我们在此报告一个新的p53诱导基因的克隆,命名为PAG608。PAG608转录物以p53依赖的方式被DNA损伤诱导。PAG608编码一种核锌指蛋白,当在转染细胞中适度表达时,它似乎优先定位于核仁。PAG608在人肿瘤衍生细胞中的瞬时过表达导致核形态发生明显变化,并可促进细胞凋亡。因此,与其他p53靶基因一起,PAG608可能在介导p53的生物学活性中发挥作用。