Inhibition of HDM2 and activation of p53 by ribosomal protein L23
Inhibition of HDM2 and activation of p53 by ribosomal protein L23
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DOI：
10.1128/mcb.24.17.7669-7680.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Jin, A;Itahana, K;Zhang, Y
细胞生长与增殖协调的重要性早已被认识到。然而，这种关系的分子基础却知之甚少。在这里，我们表明，核糖体蛋白L23与HDM2相互作用。这种相互作用涉及HDM2的中心酸性结构域和L23的N-末端结构域。L23和L11，另一种HDM2相互作用的核糖体蛋白，可以同时但不同地与HDM2相互作用在一起，形成三元复合物。我们发现，当过表达时，L23抑制HDM2诱导的p53多聚泛素化和降解，并导致p53依赖性细胞周期停滞。另一方面，敲低L23引起核仁应激并触发B23从核仁易位到核质，导致p53的稳定和活化。我们的数据表明，细胞在正常生长过程中可能会保持L23的稳态水平;改变L23的水平以响应不断变化的生长条件可能会通过中断核仁的完整性来影响HDM2-p53通路。
The importance of coordinating cell growth with proliferation has been recognized for a long time. The molecular basis of this relationship, however, is poorly understood. Here we show that the ribosomal protein L23 interacts with HDM2. The interaction involves the central acidic domain of HDM2 and an N-terminal domain of L23. L23 and L11, another HDM2-interacting ribosomal protein, can simultaneously yet distinctly interact with HDM2 together to form a ternary complex. We show that, when overexpressed, L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest. On the other hand, knocking down L23 causes nucleolar stress and triggers translocation of B23 from the nucleolus to the nucleoplasm, leading to stabilization and activation of p53. Our data suggest that cells may maintain a steady-state level of L23 during normal growth; alternating the levels of L23 in response to changing growth conditions could impinge on the HDM2-p53 pathway by interrupting the integrity of the nucleolus.