ArticleMolecular and cellular biology2009
Cdk2 and Cdk4 activities are dispensable for tumorigenesis caused by the loss of p53.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- MicroRNA-148a TargetsInternational journal of molecular sciences · 2024Article
- Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.International journal of molecular sciences · 2024Article
- The Tumor Microenvironment: Signal Transduction.Biomolecules · 2024Review
- Predicting phase-I metabolism of piceatannol: an in silico study.In silico pharmacology · 2024Article
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- Role of cyclin-dependent kinase 2 in the progression of mouse juvenile cystic kidney disease.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Identifying Hepatocellular Carcinoma Driver Genes by Integrative Pathway Crosstalk and Protein Interaction Network.DNA and cell biology · 2019Article
- MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21.Science translational medicine · 2019Article
- Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality.Oncogene · 2019Article
- [Screening of biomarkers related with leukocyte responses early after burn injury in mice by differential gene expression profiling].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Article
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- Cdk2 catalytic activity is essential for meiotic cell division in vivo.The Biochemical journal · 2016Article
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- A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis.The Journal of clinical investigation · 2014Article
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- In vitro growth inhibition of human cancer cells by novel honokiol analogs.Bioorganic & medicinal chemistry · 2012Article
- Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
The loss of p53 induces spontaneous tumors in mice, and p53 mutations are found in approximately 50% of human tumors. These tumors are generally caused by a number of events, including genomic instability, checkpoint defects, mitotic defects, deregulation of transcriptional targets, impaired apoptosis, and G(1) deregulation or a combination of these effects. In order to determine the role of proteins involved in G(1) control in tumorigenesis, we focused on Cdk2 and Cdk4, two cyclin-dependent kinases that in association with cyclin E and cyclin D promote the G(1)/S phase transition. We analyzed the consequence of loss of Cdk2 in p53-null animals by generating Cdk2(-/-) p53(-/-) mice. These mice are viable and developed spontaneous tumors, predominantly lymphoblastic lymphomas, similar to p53(-/-) mice. In contrast, the genotypes Cdk4(-/-) p53(-/-) were mostly lethal, with few exceptions, and Cdk2(-/-) Cdk4(-/-) p53(-/-) mice die during embryogenesis at embryonic day 13.5. To study the oncogenic potential, we generated mouse embryonic fibroblasts (MEFs) and found that p53(-/-), Cdk2(-/-) p53(-/-), Cdk4(-/-) p53(-/-), and Cdk2(-/-) Cdk4(-/-) p53(-/-) MEFs grew at similar rates without entering senescence. Ras-transformed MEFs of these genotypes were able to form colonies in vitro and induce tumors in nude mice. Our results suggest that tumorigenicity mediated by p53 loss does not require either Cdk2 or Cdk4, which necessitates considering the use of broad-spectrum cell cycle inhibitors as a means of effective anti-Cdk cancer therapy.
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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.