期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 298, 期 2, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2021.101524
关键词
-
资金
- National Key Research and Development Program of China [2016YFA0500304]
- NSFC [81772922, 82002917, 82030090]
- Science and Technology Program of Guangzhou [202002020092, 2020M683037]
RBM28 is an RNA-binding protein that regulates tumor progression and is associated with poor prognosis. It promotes the survival and growth of cancer cells by inhibiting the transcriptional activity of the tumor suppressor protein p53. Additionally, it translocates from the nucleolus to the nucleoplasm in response to chemotherapy drugs, likely through phosphorylation at Ser122.
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 trans-located 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据