ArticleOncogene2012
JAK2(V617F) negatively regulates p53 stabilization by enhancing MDM2 via La expression in myeloproliferative neoplasms.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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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
66 citing papers in PubMed, 114 citations in OpenAlex.
- Trial
- KT-253, a highly potent and selective MDM2 protein degrader, eliminates malignant myelofibrosis stem/progenitor cells.Leukemia · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- Isolated del(5q) with myeloproliferative driver mutations: A systematic review of published cases and clinical implications.Therapeutic advances in hematology · 2026Review
- Chinese holly fruit inhibits melanoma cell proliferation and immune escape by activating P53-P21 signaling and inhibiting JAK2-STAT1 signaling.Frontiers in nutrition · 2026Article
- Order-of-Mutation Effects on Cancer Progression: Models for Myeloproliferative Neoplasm.Bulletin of mathematical biology · 2024Article
- Calreticulin and JAK2V617F driver mutations induce distinct mitotic defects in myeloproliferative neoplasms.Scientific reports · 2024Article
- Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms.Blood cancer journal · 2024Article
- Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023Review
- Novel therapeutics for myelofibrosis.Blood research · 2023Review
- Biological drivers of clinical phenotype in myelofibrosis.Leukemia · 2023Review
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- Treating accelerated and blast phase myeloproliferative neoplasms: progress and challenges.Therapeutic advances in hematology · 2023Review
- Advances in Risk Stratification and Treatment of Polycythemia Vera and Essential Thrombocythemia.Current hematologic malignancy reports · 2022Review
- Novel Therapies in Myelofibrosis: Beyond JAK Inhibitors.Current hematologic malignancy reports · 2022Review
- The RNA-binding protein La/SSB associates with radiation-induced DNA double-strand breaks in lung cancer cell lines.Cancer reports (Hoboken, N.J.) · 2022Article
- Molecular Pathogenesis of Myeloproliferative Neoplasms: From Molecular Landscape to Therapeutic Implications.International journal of molecular sciences · 2022Review
- Combined Drug Targeting of p53-dependent and -independent Pathways Depletes Myelofibrosis Hematopoietic Stem/Progenitor Cells.Leukemia · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
JAK2(V617F) is a gain of function mutation that promotes cytokine-independent growth of myeloid cells and accounts for a majority of myeloproliferative neoplasms (MPN). Mutations in p53 are rarely found in these diseases before acute leukemia transformation, but this does not rule out a role for p53 deregulation in disease progression. Using Ba/F3-EPOR cells and ex vivo cultured CD34(+) cells from MPN patients, we demonstrate that expression of JAK2(V617F) affected the p53 response to DNA damage. We show that E3 ubiquitin ligase MDM2 accumulated in these cells, due to an increased translation of MDM2 mRNA. Accumulation of the La autoantigen, which interacts with MDM2 mRNA and promotes its translation, was responsible for the increase in MDM2 protein level and the subsequent degradation of p53 after DNA damage. Downregulation of La protein or cell treatment with nutlin-3, a MDM2 antagonist, restored the p53 response to DNA damage and the cytokine-dependence of Ba/F3-EPOR-JAK2(V617F) cells. Altogether, these data indicate that the JAK2(V617F) mutation affects p53 response to DNA damage through the upregulation of La antigen and accumulation of MDM2. They also suggest that p53 functional inactivation accounts for the cytokine hypersensitivity of JAK2(V617F) MPN and might have a role in disease progression.
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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.