ArticleThe Journal of biological chemistry2008
Elevated levels of oncogenic protein kinase Pim-1 induce the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 81 citations in OpenAlex.
- PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications.Leukemia · 2026Review
- PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.Current topics in medicinal chemistry · 2024Review
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- PIM Kinases in Multiple Myeloma.Cancers · 2021Review
- Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer.Cell death discovery · 2020Review
- Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.Oncogene · 2020Article
- The Oncogene PIM1 Contributes to Cellular Senescence by Phosphorylating Staphylococcal Nuclease Domain-Containing Protein 1 (SND1).Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- PIM kinase inhibitor, AZD1208, inhibits protein translation and induces autophagy in primary chronic lymphocytic leukemia cells.Oncotarget · 2019Article
- Considering the Role of Murine Double Minute 2 in the Cardiovascular System?Frontiers in cell and developmental biology · 2019Review
- Downregulation of Pim-2 induces cell cycle arrest in the GOncology letters · 2018Article
- RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia.Leukemia · 2018Article
- Article
- A functional SUMO-motif in the active site of PIM1 promotes its degradation via RNF4, and stimulates protein kinase activity.Scientific reports · 2017Article
- A positive feedback loop between Pim-1 kinase and HBP1 transcription factor contributes to hydrogen peroxide-induced premature senescence and apoptosis.The Journal of biological chemistry · 2017Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Pim-1 kinase as cancer drug target: An update.Biomedical reports · 2016Article
- Combination of Pim kinase inhibitors and Bcl-2 antagonists in chronic lymphocytic leukemia cells.Leukemia & lymphoma · 2016Article
- Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas.Molecular cancer · 2015Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutation of the p53 gene is a common event during tumor pathogenesis. Other mechanisms, such as mdm2 amplification, provide alternative routes through which dysfunction of the p53 pathway is promoted. Here, we address the hypothesis that elevated expression of pim oncogenes might suppress p53 by regulating Mdm2. At a physiological level, we show that endogenous Pim-1 and Pim-2 interact with endogenous Mdm2. Additionally, the Pim kinases phosphorylate Mdm2 in vitro and in cultured cells at Ser(166) and Ser(186), two previously identified targets of other signaling pathways, including Akt. Surprisingly, at high levels of Pim expression, as would occur in tumors, active, but not inactive, Pim-1 or Pim-2 blocks the degradation of both p53 and Mdm2 in a manner that is independent of Mdm2 phosphorylation, leading to increased p53 levels and, proportionately, p53-dependent transactivation. Additionally, Pim-1 induces endogenous ARF, p53, Mdm2, and p21 in primary murine embryo fibroblasts and stimulates senescence-associated beta-galactosidase levels, consistent with the induction of senescence. Immunohistochemical analysis of a cohort of 33 human mantle cell lymphomas shows that elevated expression of Pim-1 occurs in 42% of cases, with elevated Pim-2 occurring in 9% of cases, all of which also express Pim-1. Notably, elevated Pim-1 correlates with elevated Mdm2 in MCL with a p value of 0.003. Taken together, our data are consistent with the idea that Pim normally interacts with the p53 pathway but, when expressed at pathological levels, behaves as a classic dominant oncogene that stimulates a protective response through induction of the p53 pathway.
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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.