Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition
Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition
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DOI：
10.1128/mcb.24.17.7654-7668.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Lu, H
中科院分区：
文献类型：
--
作者：
Dai, MS;Zeng, SX;Lu, H
p53-MDM2 反馈环路对于细胞生长控制至关重要，并受到多种调控以响应各种应激信号。在这里，我们报告了该循环的另一个调节器。使用免疫亲和方法，我们纯化了含有核糖体蛋白 L23 的 MDM2 相关蛋白复合物。 L23与MDM2相互作用，形成独立于80S核糖体和多核糖体的复合物。 L23 与 MDM2 的相互作用通过放线菌素 D 处理得到增强，但不是通过 γ 射线照射得到增强，从而导致 p53 激活。这种激活被针对 L23 的小干扰 RNA 抑制。 L23 的异位表达减少了 MDM2 介导的 p53 泛素化，并在 p53 丰富的 U2OS 细胞中诱导 p53 活性和 G(1) 阻滞，但在 p53 缺陷的 Saos-2 细胞中则不然。这些结果表明 L23 是 p53-MDM2 反馈调节的另一个调节因子。
The p53-MDM2 feedback loop is vital for cell growth control and is subjected to multiple regulations in response to various stress signals. Here we report another regulator of this loop. Using an immunoaffinity method, we purified an MDM2-associated protein complex that contains the ribosomal protein L23. L23 interacted with MDM2, forming a complex independent of the 80S ribosome and polysome. The interaction of L23 with MDM2 was enhanced by treatment with actinomycin D but not by gamma-irradiation, leading to p53 activation. This activation was inhibited by small interfering RNA against L23. Ectopic expression of L23 reduced MDM2-mediated p53 ubiquitination and also induced p53 activity and G(1) arrest in p53-proficient U2OS cells but not in p53-deficient Saos-2 cells. These results reveal that L23 is another regulator of the p53-MDM2 feedback regulation.