RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53.
RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53.
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RNA结合蛋白RBM28可以从核仁转位至核质，抑制p53的转录活性。
DOI：
10.1016/j.jbc.2021.101524
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Lin X;Zhou L;Zhong J;Zhong L;Zhang R;Kang T;Wu Y
rna结合蛋白RBM28 （RBM28）作为剪接体小核核糖核蛋白的核仁组分，参与核仁应激反应。RBM28是否以及如何调节肿瘤进展尚不清楚。在这里，我们报道RBM28在各种类型的癌症中经常过表达，并且其上调与不良预后相关。功能和机制分析显示，RBM28通过与肿瘤抑制因子p53的dna结合域相互作用，抑制p53的转录活性，从而促进癌细胞的生存和生长。在接受化疗药物（如阿霉素）治疗后，RBM28从核核转移到核质，这可能是通过DNA检查点激酶1和2 （Chk1/2）在Ser122位点磷酸化RBM28介导的，表明RBM28可能作为核核应激传感器响应DNA损伤应激。我们的研究结果不仅揭示了RBM28作为癌症的潜在生物标志物和治疗靶点，而且还提供了癌细胞如何将应激信号转化为连接核核和肿瘤抑制因子p53调节的细胞反应的机制见解。
RNA-binding protein RBM28 (RBM28), as a nucleolar component of spliceosomal small nuclear ribonucleoproteins, is involved in the nucleolar stress response. Whether and how RBM28 regulates tumor progression remains unclear. Here, we report that RBM28 is frequently overexpressed in various types of cancer and that its upregulation is associated with a poor prognosis. Functional and mechanistic assays revealed that RBM28 promotes the survival and growth of cancer cells by interacting with the DNA-binding domain of tumor suppressor p53 to inhibit p53 transcriptional activity. Upon treatment with chemotherapeutic drugs (e.g., adriamycin), RBM28 is translocated from the nucleolus to the nucleoplasm, which is likely mediated via phosphorylation of RBM28 at Ser122 by DNA checkpoint kinases 1 and 2 (Chk1/2), indicating that RBM28 may act as a nucleolar stress sensor in response to DNA damage stress. Our findings not only reveal RBM28 as a potential biomarker and therapeutic target for cancers but also provide mechanistic insights into how cancer cells convert stress signals into a cellular response linking the nucleolus to regulation of the tumor suppressor p53.
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