ArticleThe Journal of biological chemistry2012
Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 66 citations in OpenAlex.
- MiR-4725-3p acts as an oncogene and prognostic biomarker in hepatocellular carcinoma.World journal of surgical oncology · 2026Article
- NPM3 as an Unfavorable Prognostic Biomarker Involved in Oncogenic Pathways of Lung AdenocarcinomaCombinatorial chemistry & high throughput screening · 2024Article
- SUMO Proteomics Analyses Identify Protein Inhibitor of Activated STAT-Mediated Regulatory Networks Involved in Cell Cycle and Cell Proliferation.Journal of proteome research · 2023Article
- Review
- Advancements in Activating Transcription Factor 5 Function in Regulating Cell Stress and Survival.International journal of molecular sciences · 2022Review
- Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.International journal of molecular sciences · 2022Review
- A role for the NPM1/PTPN14/YAP axis in mediating hypoxia-induced chemoresistance to sorafenib in hepatocellular carcinoma.Cancer cell international · 2022Article
- Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro.Journal of translational medicine · 2022Article
- BZW2/5MP1 acts as a promising target in hepatocellular carcinoma.Journal of Cancer · 2021Article
- NPM1 Biology in Myeloid Neoplasia.Current hematologic malignancy reports · 2020Review
- Article
- Review
- Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.World journal of gastrointestinal oncology · 2018Review
- SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome.The Journal of biological chemistry · 2018Article
- The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer.Oncotarget · 2017Review
- Targeting ATF5 in Cancer.Trends in cancer · 2017Article
- Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.World journal of gastroenterology · 2017Article
- Nucleophosmin: from structure and function to disease development.BMC molecular biology · 2016Review
- Association between human cytomegalovirus infection and histone acetylation level in various histological types of glioma.Oncology letters · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Nucleophosmin (NPM1/B23) and the activating transcription factor 5 (ATF5) are both known to subject to cell type-dependent regulation. NPM1 is expressed weakly in hepatocytes and highly expressed in hepatocellular carcinomas (HCC) with a clear correlation between enhanced NPM1 expression and increased tumor grading and poor prognosis, whereas in contrast, ATF5 is expressed abundantly in hepatocytes and down-regulated in HCC. Re-expression of ATF5 in HCC inhibits cell proliferation. We report here that using an unbiased approach, tandem affinity purification (TAP) followed with mass spectrometry (MS), we identified NPM1 as a novel ATF5-interacting protein. Unlike many other NPM1-interacting proteins that interact with the N-terminal oligomerization domain of NPM1, ATF5 binds via its basic leucine zipper to the C-terminal region of NPM1 where its nucleolar localization signal is located. NPM1 association with ATF5, whose staining patterns partially overlap in the nucleoli, promotes ATF5 protein degradation through proteasome-dependent and caspase-dependent pathways. NPM1-c, a mutant NPM1 that is defective in nucleolar localization, failed to stimulate ATF5 polyubiquitination and was unable to down-regulate ATF5. NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein. NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. Our study establishes a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC.
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