A ribonucleotide reductase gene is a transcriptional target of p53 and p73
A ribonucleotide reductase gene is a transcriptional target of p53 and p73
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DOI：
10.1038/sj.onc.1203774
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发表时间：
2000-08-31
期刊：
影响因子：
8
通讯作者：
Vousden, KH
中科院分区：
文献类型：
--
作者：
Nakano, K;Bálint, É;Vousden, KH
已鉴定出许多 p53 诱导基因可能在介导 p53 的各种下游活动中发挥作用，我们鉴定了核糖核苷酸还原酶的近亲，最近命名为 p53R2，作为 p53 诱导基因，并表明该基因被激活 p53 反应的几种应激信号激活，包括 DNA 损伤剂和 p14（ARF），p53R2 表达是由有缺陷的 p53 突变体诱导的细胞凋亡，但保留细胞周期阻滞功能，尽管没有观察到 p53R2 响应 p21(WAF1/CIP1) 介导的细胞周期阻滞而诱导。 p53 家族成员 p73 的几种亚型也被证明可诱导 p53R2 表达。野生型 p53R2 或靶向细胞核的 p53R2 的瞬时异位表达不会显着改变未应激细胞中的细胞周期进程。将该基因鉴定为 p53 靶标支持 p53 除了抑制受损细胞的生长之外，在 DNA 修复中发挥直接作用。
Many p53-inducible genes have been identified that might play a role in mediating the various downstream activities of p53, We have identified a close relative of ribonucleotide reductase, recently named p53R2, as a p53-inducible gene, and show that this gene is activated by several stress signals that activate a p53 response, including DNA damaging agents and p14(ARF), p53R2 expression was induced by p53 mutants that are defective for the activation of apoptosis, but retain cell cycle arrest function, although no induction of p53R2 was seen in response to p21(WAF1/CIP1)-mediated cell cycle arrest. Several isoforms of the p53 family member p73 were also shown to induce p53R2 expression. Transient ectopic expression of either wild type p53R2 or p53R2 targeted to the nucleus, did not significantly alter cell cycle progression in unstressed cells, The identification of this gene as a p53 target supports a direct role for p53 in DNA repair, in addition to inhibition of growth of damaged cells.