دورية أكاديمية
RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53.
| العنوان: | RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53. |
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| المؤلفون: | Lin X; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Zhou L; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Zhong J; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Zhong L; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China., Zhang R; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Kang T; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: kangtb@sysucc.org.cn., Wu Y; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: wuyzh@sysucc.org.cn. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Feb; Vol. 298 (2), pp. 101524. Date of Electronic Publication: 2021 Dec 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | RNA-Binding Proteins*/genetics , RNA-Binding Proteins*/metabolism , Tumor Suppressor Protein p53*/genetics , Tumor Suppressor Protein p53*/metabolism, Cell Line, Tumor ; Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Humans ; Ribonucleoproteins, Small Nuclear/metabolism ; Transcription, Genetic |
| مستخلص: | 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. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Chk1; Chk2; RBM28; nucleolar stress; p53; phosphorylation |
| المشرفين على المادة: | 0 (RBM28 protein, human) 0 (RNA-Binding Proteins) 0 (Ribonucleoproteins, Small Nuclear) 0 (TP53 protein, human) 0 (Tumor Suppressor Protein p53) |
| تواريخ الأحداث: | Date Created: 20211226 Date Completed: 20220428 Latest Revision: 20220531 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8789582 |
| DOI: | 10.1016/j.jbc.2021.101524 |
| PMID: | 34953860 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2021.101524 |