Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway
Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway
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DOI：
10.1038/onc.2008.189
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发表时间：
2008-10-02
期刊：
影响因子：
8
通讯作者：
Vousden, K. H.
中科院分区：
文献类型：
--
作者：
Horn, H. F.;Vousden, K. H.
MDM2是一种泛素连接酶，在调节p53肿瘤抑制蛋白的稳定性中起关键作用。几种蛋白质已被证明通过与MDM 2的E3功能相互作用并抑制MDM 2的E3功能来激活p53途径，从而导致p53的积累。这些包括交替阅读框（ARF）蛋白和核糖体蛋白L5和L11。我们发现，当单独过表达时，L11在抑制MDM2方面的效力远低于p14（ARF）。然而，L11与L5合作，导致MDM2的E3活性的强烈抑制，以及接近p14（ARF）实现的p53的稳定和活化。我们进一步表明，L11结合5S rRNA的能力对于与L5的合作是重要的，并且不能结合5S rRNA的突变体L11不能与L5合作抑制MDM2。
MDM2 is a ubiquitin ligase that plays a key role in regulating the stability of the p53 tumor suppressor protein. Several proteins have been shown to activate the p53 pathway by interacting with and inhibiting the E3 function of MDM2, thereby leading to an accumulation of p53. These include the alternate reading frame (ARF) proteins and the ribosomal proteins L5 and L11. We found that when overexpressed alone, L11 is much less potent in inhibiting MDM2 than p14(ARF). However, L11 cooperates with L5, resulting in a robust inhibition of the E3 activity of MDM2, and a stabilization and activation of p53 approaching that achieved by p14(ARF). We further showed that the ability of L11 to bind the 5S rRNA is important for the cooperation with L5, and a mutant L11, which cannot bind the 5S rRNA, cannot cooperate with L5 in inhibiting MDM2.