在经历V(D)J重组的细胞中，Miz-1通过核糖体蛋白L22调节Trp53的翻译。
Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination.
作者信息
Rashkovan Marissa, Vadnais Charles, Ross Julie, Gigoux Mathieu, Suh Woong-Kyung, Gu Wei, Kosan Christian, Möröy Tarik
机构信息
Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7; Division of Experimental Medicine, McGill University, Montréal, QC, Canada H3A 1A3;
Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7;
出版信息
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5411-9. doi: 10.1073/pnas.1412107111. Epub 2014 Dec 2.
To be effective, the adaptive immune response requires a large repertoire of antigen receptors, which are generated through V(D)J recombination in lymphoid precursors. These precursors must be protected from DNA damage-induced cell death, however, because V(D)J recombination generates double-strand breaks and may activate p53. Here we show that the BTB/POZ domain protein Miz-1 restricts p53-dependent induction of apoptosis in both pro-B and DN3a pre-T cells that actively rearrange antigen receptor genes. Miz-1 exerts this function by directly activating the gene for ribosomal protein L22 (Rpl22), which binds to p53 mRNA and negatively regulates its translation. This mechanism limits p53 expression levels and thus contains its apoptosis-inducing functions in lymphocytes, precisely at differentiation stages in which V(D)J recombination occurs.
为了发挥作用，适应性免疫反应需要大量的抗原受体库，这些受体是通过淋巴前体细胞中的V(D)J重组产生的。然而，这些前体细胞必须受到保护，以免因DNA损伤诱导细胞死亡，因为V(D)J重组会产生双链断裂并可能激活p53。我们在此表明，BTB/POZ结构域蛋白Miz-1在积极重排抗原受体基因的前B细胞和DN3a前T细胞中，限制p53依赖的凋亡诱导。Miz-1通过直接激活核糖体蛋白L22（Rpl22）的基因发挥此功能，Rpl22与p53 mRNA结合并负调节其翻译。这种机制限制了p53的表达水平，从而在淋巴细胞中抑制其凋亡诱导功能，特别是在发生V(D)J重组的分化阶段。
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