核孔蛋白 Nup155 是肝癌中 p53 网络的一部分。

Nucleoporin Nup155 is part of the p53 network in liver cancer.

机构信息

Institute of Pathology, University Hospital Heidelberg, 69120, Heidelberg, Germany.

Institute of Pathology, University Medicine Greifswald, 17475, Greifswald, Germany.

出版信息

Nat Commun. 2019 May 14;10(1):2147. doi: 10.1038/s41467-019-10133-z.

Cancer-relevant signalling pathways rely on bidirectional nucleocytoplasmic transport events through the nuclear pore complex (NPC). However, mechanisms by which individual NPC components (Nups) participate in the regulation of these pathways remain poorly understood. We discover by integrating large scale proteomics, polysome fractionation and a focused RNAi approach that Nup155 controls mRNA translation of p21 (CDKN1A), a key mediator of the p53 response. The underlying mechanism involves transcriptional regulation of the putative tRNA and rRNA methyltransferase FTSJ1 by Nup155. Furthermore, we observe that Nup155 and FTSJ1 are p53 repression targets and accordingly find a correlation between the p53 status, Nup155 and FTSJ1 expression in murine and human hepatocellular carcinoma. Our data suggest an unanticipated regulatory network linking translational control by and repression of a structural NPC component modulating the p53 pathway through its effectors.

癌症相关信号通路依赖于通过核孔复合物（NPC）的双向核质转运事件。然而，个别 NPC 成分（Nups）参与这些通路的调节的机制仍知之甚少。我们通过整合大规模蛋白质组学、多核糖体分离和聚焦的 RNAi 方法发现，Nup155 控制着 p21（CDKN1A）的 mRNA 翻译，p21 是 p53 反应的关键介质。潜在的机制涉及 Nup155 对假定的 tRNA 和 rRNA 甲基转移酶 FTSJ1 的转录调控。此外，我们观察到 Nup155 和 FTSJ1 是 p53 抑制靶点，因此在鼠和人肝癌中发现了 p53 状态、Nup155 和 FTSJ1 表达之间的相关性。我们的数据表明，通过其效应物，一种结构 NPC 成分的调节 p53 通路的抑制和翻译控制之间存在一个意想不到的调节网络。