ArticleThe Journal of clinical investigation2014
CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
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- CDK4: a master regulator of the cell cycle and its role in cancer.Genes & cancer · 2022Review
- Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation.Cancer discovery · 2021Article
- Forkhead Box Protein O1: Functional Diversity and Post-Translational Modification, a New Therapeutic Target?Drug design, development and therapy · 2021Review
- MAGI2-AS3 suppresses MYC signaling to inhibit cell proliferation and migration in ovarian cancer through targeting miR-525-5p/MXD1 axis.Cancer medicine · 2020Article
- Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1.The Journal of biological chemistry · 2020Article
- Mouse Models ofFrontiers in immunology · 2020Review
- FHIT and C-MYC expression in cervical histology and cytology as biomarkers for detecting high-grade intraepithelial neoplasia in human papillomavirus-positive women.Cancer biomarkers : section A of Disease markers · 2020Article
- Article
- Article
- The Complex Interplay between DNA Injury and Repair in Enzymatically Induced Mutagenesis and DNA Damage in B Lymphocytes.International journal of molecular sciences · 2017Review
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- Therapeutic targeting of replicative immortality.Seminars in cancer biology · 2015Review
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
The G1 kinase CDK4 is amplified or overexpressed in some human tumors and promotes tumorigenesis by inhibiting known tumor suppressors. Here, we report that CDK4 deficiency markedly accelerated lymphoma development in the Eμ-Myc transgenic mouse model of B lymphoma and that silencing or loss of CDK4 augmented the tumorigenic potential of Myc-driven mouse and human B cell lymphoma in transplant models. Accelerated disease in CDK4-deficient Eμ-Myc transgenic mice was associated with rampant genomic instability that was provoked by dysregulation of a FOXO1/RAG1/RAG2 pathway. Specifically, CDK4 phosphorylated and inactivated FOXO1, which prevented FOXO1-dependent induction of Rag1 and Rag2 transcription. CDK4-deficient Eμ-Myc B cells had high levels of the active form of FOXO1 and elevated RAG1 and RAG2. Furthermore, overexpression of RAG1 and RAG2 accelerated lymphoma development in a transplant model, with RAG1/2-expressing tumors exhibiting hallmarks of genomic instability. Evaluation of human tumor samples revealed that CDK4 expression was markedly suppressed, while FOXO1 expression was elevated, in several subtypes of human non-Hodgkin B cell lymphoma. Collectively, these findings establish a context-specific tumor suppressor function for CDK4 that prevents genomic instability, which contributes to B cell lymphoma. Furthermore, our data suggest that targeting CDK4 may increase the risk for the development and/or progression of lymphoma.
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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.