RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibit the transcriptional activity of p53

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:298

Enthalten in:

The Journal of biological chemistry - 298(2022), 2 vom: 15. Feb., Seite 101524

Sprache:

Englisch

Beteiligte Personen:

Lin, Xin [VerfasserIn]
Zhou, Liwen [VerfasserIn]
Zhong, Jianliang [VerfasserIn]
Zhong, Li [VerfasserIn]
Zhang, Ruhua [VerfasserIn]
Kang, Tiebang [VerfasserIn]
Wu, Yuanzhong [VerfasserIn]

Links:

Volltext

Themen:

Chk1
Chk2
Journal Article
Nucleolar stress
P53
Phosphorylation
RBM28
RBM28 protein, human
RNA-Binding Proteins
Research Support, Non-U.S. Gov't
Ribonucleoproteins, Small Nuclear
TP53 protein, human
Tumor Suppressor Protein p53

Anmerkungen:

Date Completed 28.04.2022

Date Revised 31.05.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jbc.2021.101524

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334897556