Normandie Univ, INSERM UMR1245, UNICAEN, Caen, France.
Université Paris-Descartes, Paris, France.
Cell Signal. 2018 Jun;46:76-82. doi: 10.1016/j.cellsig.2018.02.016. Epub 2018 Mar 1.
Primary mediastinal B-cell lymphoma (PMBL) is a distinct B-cell lymphoma subtype with unique clinicopathological and molecular features. PMBL cells are characterised by several genetic abnormalities that conduct to the constitutive activation of the Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signalling pathway. Among recurrent genetic changes in PMBL, we previously reported that the XPO1 gene encoding exportin 1 that controls the nuclear export of cargo proteins and RNAs, is mutated (p.E571K) in about 25% of PMBL cases. We therefore hypothesized that STAT6 could be a cargo of XPO1 and that STAT6 cytoplasm/nucleus shuttle could be altered in a subset of PMBL cells. Using immunocytochemistry techniques as well as the proximity ligation assay, we showed that STAT6 bound XPO1 in PBML cell lines and in HEK-293 cells genetically engineered to produce STAT6. Moreover, XPO1-mediated export of STAT6 occurs in cells expressing either a wild-type or the E571K mutated XPO1 protein.
原发性纵隔 B 细胞淋巴瘤（PMBL）是一种具有独特临床病理和分子特征的 B 细胞淋巴瘤亚型。PMBL 细胞的特征是存在几种遗传异常，导致 Janus 激酶 2/信号转导和转录激活因子 6（JAK2/STAT6）信号通路的组成性激活。在 PMBL 的反复出现的遗传变化中，我们之前报道过，编码控制货物蛋白和 RNA 核输出的输出蛋白 1 的 XPO1 基因在大约 25%的 PMBL 病例中发生突变（p.E571K）。因此，我们假设 STAT6 可能是 XPO1 的货物，并且 STAT6 的细胞质/核穿梭可能在一部分 PMBL 细胞中发生改变。我们使用免疫细胞化学技术和邻近连接测定法，证明 STAT6 在 PMBL 细胞系和遗传工程表达 STAT6 的 HEK-293 细胞中与 XPO1 结合。此外，表达野生型或 E571K 突变 XPO1 蛋白的细胞中都存在 XPO1 介导的 STAT6 输出。
