Lin Y, Ma W, Benchimol S
Ontario Cancer Institute/Princess Margaret Hospital and the Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Nat Genet. 2000 Sep;26(1):122-7. doi: 10.1038/79102.
The p53 tumour suppressor promotes cell-cycle arrest or apoptosis in response to cellular stress, such as DNA damage and oncogenesis. This role of p53 is important for its tumour-suppression function and depends, at least in part, on its ability to bind to specific DNA sequences and activate the transcription of target genes. The pathway through which p53 promotes apoptosis is not fully understood. Here we describe a new gene regulated by p53 that encodes a predicted protein of 915 amino acids in mice (910 amino acids in humans), which we have named Pidd. The mouse Pidd cDNA contains a p53 consensus DNA binding sequence upstream of the Pidd-coding region. This sequence element bound to p53 and conferred p53-dependent inducibility on a heterologous reporter gene. Moreover, Pidd RNA was induced by ionizing radiation in a p53-dependent manner and the basal level of Pidd RNA was dependent on Trp53 status. Overexpression of Pidd inhibited cell growth in a p53-like manner by inducing apoptosis. Antisense inhibition of Pidd expression attenuated p53-mediated apoptosis. Our data suggest that Pidd is an effector of p53-dependent apoptosis.
p53肿瘤抑制因子可响应细胞应激（如DNA损伤和肿瘤发生）促进细胞周期停滞或凋亡。p53的这一作用对其肿瘤抑制功能很重要，并且至少部分取决于其结合特定DNA序列并激活靶基因转录的能力。p53促进凋亡的途径尚未完全阐明。在此，我们描述了一个受p53调控的新基因，该基因在小鼠中编码一个预测含915个氨基酸的蛋白质（在人类中为910个氨基酸），我们将其命名为Pidd。小鼠Pidd cDNA在Pidd编码区上游含有一个p53共有DNA结合序列。该序列元件与p53结合，并赋予异源报告基因p53依赖性诱导性。此外，Pidd RNA以p53依赖性方式被电离辐射诱导，且Pidd RNA的基础水平取决于Trp53状态。Pidd的过表达通过诱导凋亡以类似p53的方式抑制细胞生长。对Pidd表达的反义抑制减弱了p53介导的凋亡。我们的数据表明，Pidd是p53依赖性凋亡的一个效应因子。
