AML-associated mutation of nucleophosmin compromises its interaction with nucleolin
- PMID: 30130654
- DOI: 10.1016/j.biocel.2018.08.008
AML-associated mutation of nucleophosmin compromises its interaction with nucleolin
Abstract
C-terminal mutations of the nucleolar protein nucleophosmin (NPM) are the most frequent genetic aberration detected in acute myeloid leukemia (AML) with normal karyotype. The mutations cause aberrant cytoplasmic localization of NPM and lead to loss of functions associated with NPM nucleolar localization, e.g. in ribosome biogenesis or DNA-damage repair. NPM has many interaction partners and some of them were proved to interact also with the mutated form (NPMmut) and due to this interaction thereby to be withdrawn from their site of action. We analyzed the impact of the mutation on NPM interaction with nucleolin (NCL) which is also prevalently localized into the nucleolus and cooperates with wild-type NPM (NPMwt) in many cellular processes. We revealed that the NCL-NPM complex formation is completely abolished by the mutation and that the presence/absence of the interaction is not affected by drugs causing genotoxic stress or differentiation. Deregulation resulting from changes of NCL/NPMwt ratio may contribute to leukemogenesis.
Keywords: AML; Interaction; Mutation; Nucleolin; Nucleophosmin; Oligomerization.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Similar articles
-
Nucleophosmin in leukemia: Consequences of anchor loss.Int J Biochem Cell Biol. 2019 Jun;111:52-62. doi: 10.1016/j.biocel.2019.04.007. Epub 2019 Apr 19. Int J Biochem Cell Biol. 2019. PMID: 31009764 Review.
-
Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM.PLoS One. 2017 Apr 6;12(4):e0175175. doi: 10.1371/journal.pone.0175175. eCollection 2017. PLoS One. 2017. PMID: 28384310 Free PMC article.
-
Low-Dose Actinomycin-D Induces Redistribution of Wild-Type and Mutated Nucleophosmin Followed by Cell Death in Leukemic Cells.J Cell Biochem. 2016 Jun;117(6):1319-29. doi: 10.1002/jcb.25420. Epub 2015 Nov 9. J Cell Biochem. 2016. PMID: 26505272
-
Nucleolar phosphoprotein modifications as a marker of apoptosis induced by RITA treatment.Biochim Biophys Acta Mol Cell Res. 2023 Oct;1870(7):119501. doi: 10.1016/j.bbamcr.2023.119501. Epub 2023 Jun 3. Biochim Biophys Acta Mol Cell Res. 2023. PMID: 37276927
-
The roles of nucleolin subcellular localization in cancer.Biochimie. 2015 Jun;113:78-85. doi: 10.1016/j.biochi.2015.03.023. Epub 2015 Apr 9. Biochimie. 2015. PMID: 25866190 Review.
Cited by
-
Nucleolin and nucleophosmin expression patterns in pulmonary adenocarcinoma invading the pleura and in pleural malignant mesothelioma.Thorac Cancer. 2020 Sep;11(9):2529-2535. doi: 10.1111/1759-7714.13564. Epub 2020 Jul 16. Thorac Cancer. 2020. PMID: 32671956 Free PMC article.
-
RNA-Binding Proteins in Acute Leukemias.Int J Mol Sci. 2020 May 12;21(10):3409. doi: 10.3390/ijms21103409. Int J Mol Sci. 2020. PMID: 32408494 Free PMC article. Review.
-
AML-Related NPM Mutations Drive p53 Delocalization into the Cytoplasm with Possible Impact on p53-Dependent Stress Response.Cancers (Basel). 2021 Jun 29;13(13):3266. doi: 10.3390/cancers13133266. Cancers (Basel). 2021. PMID: 34209894 Free PMC article.
-
Roniciclib down-regulates stemness and inhibits cell growth by inducing nucleolar stress in neuroblastoma.Sci Rep. 2020 Jul 31;10(1):12902. doi: 10.1038/s41598-020-69499-6. Sci Rep. 2020. PMID: 32737364 Free PMC article.
-
Novel INHAT repressor drives glioblastoma growth by promoting ribosomal DNA transcription in glioma stem cells.Neuro Oncol. 2023 Aug 3;25(8):1428-1440. doi: 10.1093/neuonc/noac272. Neuro Oncol. 2023. PMID: 36521011 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous
