ArticleLeukemia2009
A dose-dependent tug of war involving the NPM1 leukaemic mutant, nucleophosmin, and ARF.
Article in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Article
- Abnormal nucleoli architecture and aggregate formation in nucleophosmin mutated acute myeloid leukaemia.Journal of cell science · 2025Article
- Review
- miR-10a as a therapeutic target and predictive biomarker for MDM2 inhibition in acute myeloid leukemia.Leukemia · 2021Article
- AML-Related NPM Mutations Drive p53 Delocalization into the Cytoplasm with Possible Impact on p53-Dependent Stress Response.Cancers · 2021Article
- NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization.Scientific reports · 2021Article
- An updated account on molecular heterogeneity of acute leukemia.American journal of blood research · 2021Review
- A comprehensive review of genetic alterations and molecular targeted therapies for the implementation of personalized medicine in acute myeloid leukemia.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Review
- New insights into the biology of acute myeloid leukemia with mutated NPM1.International journal of hematology · 2019Review
- Knockdown of nucleophosmin 1 suppresses proliferation of triple-negative breast cancer cells through activating CDH1/Skp2/p27kip1 pathway.Cancer management and research · 2019Article
- Role of Nucleophosmin Gene Mutation in Leukemogenesis of Acute Myeloid Leukemia.Journal of hematology · 2018Article
- Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ.Oncogenesis · 2017Article
- Review
- Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth.Scientific reports · 2017Article
- Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90.PloS one · 2017Article
- Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM.PloS one · 2017Article
- NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape.Scientific reports · 2015Article
- Mouse models of NPM1-mutated acute myeloid leukemia: biological and clinical implications.Leukemia · 2015Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In acute myeloid leukaemia (AML), nucleophosmin-1 (NPM1) mutations create a nuclear export signal (NES) motif and disrupt tryptophans at NPM1 C-terminus, leading to nucleophosmin accumulation in leukaemic cell cytoplasm. We investigated how nucleophosmin NES motifs (two physiological and one created by the mutation) regulate traffic and interaction of mutated NPM1, NPM1wt and p14(ARF). Nucleophosmin export into cytoplasm was maximum when the protein contained all three NES motifs, as naturally occurs in NPM1-mutated AML. The two physiological NES motifs mediated NPM1 homo/heterodimerization, influencing subcellular distribution of NPM1wt, mutated NPM1 and p14(ARF) in a 'dose-dependent tug of war' fashion. In transfected cells, excess doses of mutant NPM1 relocated completely NPM1wt (and p14(ARF)) from the nucleoli to the cytoplasm. This distribution pattern was also observed in a proportion of NPM1-mutated AML patients. In transfected cells, excess of NPM1wt (and p14(ARF)) relocated NPM1 mutant from the cytoplasm to the nucleoli. Notably, this distribution pattern was not observed in AML patients where the mutant was consistently cytoplasmic restricted. These findings reinforce the concept that NPM1 mutants are naturally selected for most efficient cytoplasmic export, pointing to this event as critical for leukaemogenesis. Moreover, they provide a rationale basis for designing small molecules acting at the interface between mutated NPM1 and other interacting proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.