ArticleCell cycle (Georgetown, Tex.)2015
Evidence for a CDK4-dependent checkpoint in a conditional model of cellular senescence.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- E2F activity determines mitosis versus whole-genome duplication in G2-arrested cells.Nature communications · 2025Article
- Senolytic Treatment Improve Small Intestine Regeneration in Aging.Aging and disease · 2024Article
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics.Frontiers in pharmacology · 2022Article
- Anti-proliferation and anti-migration effects of an aqueous extract ofPharmaceutical biology · 2020Article
- Proteomic Level Changes on Treatment in MCF-7/DDP Breast Cancer Drug- Resistant Cells.Anti-cancer agents in medicinal chemistry · 2020Article
- Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells.Journal of Cancer · 2020Article
- Effects of ABT-737 combined with irradiation treatment on uterine cervical cancer cells.Oncology letters · 2019Article
- Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.Investigational new drugs · 2019Article
- Cyclin-Dependent Kinases 4/6 Inhibitors in Breast Cancer: Current Status, Resistance, and Combination Strategies.Journal of Cancer · 2019Article
- Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles.Oncotarget · 2018Article
- Regulation of senescence escape by the cdk4-EZH2-AP2M1 pathway in response to chemotherapy.Cell death & disease · 2018Article
- Unexpected role of CDK4 in a G2/M checkpoint.Cell cycle (Georgetown, Tex.) · 2015Article
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7 authors at 2 institutions in 4 countries.
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Abstract
Cellular senescence, the stable cell cycle arrest elicited by various forms of stress, is an important facet of tumor suppression. Although much is known about the key players in the implementation of senescence, including the pRb and p53 axes and the cyclin dependent kinase inhibitors p16(INK4a) and p21(CIP1), many details remain unresolved. In studying conditional senescence in human fibroblasts that express a temperature sensitive SV40 large T-antigen (T-Ag), we uncovered an unexpected role for CDK4. At the permissive temperature, where pRb and p53 are functionally compromised by T-Ag, cyclin D-CDK4 complexes are disrupted by the high p16(INK4a) levels and reduced expression of p21(CIP1). In cells arrested at the non-permissive temperature, p21(CIP1) promotes reassembly of cyclin D-CDK4 yet pRb is in a hypo-phosphorylated state, consistent with cell cycle arrest. In exploring whether the reassembled cyclin D-CDK4-p21 complexes are functional, we found that shRNA-mediated knockdown or chemical inhibition of CDK4 prevented the increase in cell size associated with the senescent phenotype by allowing the cells to arrest in G1 rather than G2/M. The data point to a role for CDK4 kinase activity in a G2 checkpoint that contributes to senescence.
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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.