ArticleOncotarget2014
AKT regulates NPM dependent ARF localization and p53mut stability in tumors.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- Targeting breast cancer resistance protein (BCRP/ABCG2) in cancer.Translational cancer research · 2024Review
- Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis.Acta biochimica et biophysica Sinica · 2023Article
- Review
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis.Biomolecules · 2021Review
- Nucleophosmin Protein Dephosphorylation by DUSP3 Is a Fine-Tuning Regulator of p53 Signaling to Maintain Genomic Stability.Frontiers in cell and developmental biology · 2021Article
- Post-Translational Regulation of ARF: Perspective in Cancer.Biomolecules · 2020Review
- Article
- Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells.Translational oncology · 2019Article
- miR302a inhibits the proliferation of esophageal cancer cells through the MAPK and PI3K/Akt signaling pathways.Oncology letters · 2018Article
- Article
- Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2.Cell death & disease · 2016Article
- Nucleolus-derived mediators in oncogenic stress response and activation of p53-dependent pathways.Histochemistry and cell biology · 2016Review
- p53 coordinates base excision repair to prevent genomic instability.Nucleic acids research · 2016Article
- Article
- Asymmetric Modulation of Protein Order-Disorder Transitions by Phosphorylation and Partner Binding.Angewandte Chemie (International ed. in English) · 2016Article
- Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways.Oncotarget · 2015Article
- A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression.Oncogene · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status.
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Registered trials
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.