ArticleCell cycle (Georgetown, Tex.)2012
Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 91 citations in OpenAlex.
- Enzalutamide effectively inhibits the growth of meningiomas via p21-dependent senescence induction.Molecular biology reports · 2026Article
- G1/S arrest: a key mechanism of cellular aging and replicative senescence.Biogerontology · 2026Review
- MBNL loss of function in smooth muscle as a model for myotonic dystrophy associated gastrointestinal dysmotility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.Cell reports · 2025Article
- DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.bioRxiv : the preprint server for biology · 2025Article
- SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina.npj aging · 2024Article
- SNAI2 enhances HPV‑negative cervical cancer cell dormancy by modulating u‑PAR expression and the activity of the ERK/p38 signaling pathwayOncology reports · 2024Article
- BUB1, BUB1B, CCNA2, and CDCA8, along with miR-524-5p, as clinically relevant biomarkers for the diagnosis and treatment of endometrial carcinoma.BMC cancer · 2023Article
- Splicing factor SRSF3 represses translation of p21Cell death & disease · 2022Article
- Timosaponin AIII Induces G2/M Arrest and Apoptosis in Breast Cancer by Activating the ATM/Chk2 and p38 MAPK Signaling Pathways.Frontiers in pharmacology · 2020Article
- CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo.BMC cancer · 2019Article
- Heat shock protein 27 promotes cell cycle progression by down-regulating E2F transcription factor 4 and retinoblastoma family protein p130.The Journal of biological chemistry · 2018Article
- Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence.Aging · 2018Article
- Dosing time dependent in vitro pharmacodynamics of Everolimus despite a defective circadian clock.Cell cycle (Georgetown, Tex.) · 2018Article
- Rapamycin, proliferation and geroconversion to senescence.Cell cycle (Georgetown, Tex.) · 2018Article
- Cellular senescence, senescence-associated secretory phenotype, and chronic kidney disease.Oncotarget · 2017Review
- Mitotic catastrophe and cell cycle arrest are alternative cell death pathways executed by bortezomib in rituximab resistant B-cell lymphoma cells.Oncotarget · 2017Article
- Gerosuppression by pan-mTOR inhibitors.Aging · 2016Article
- Restoring miR122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy through Smad-independent TGF-β pathway.Oncotarget · 2016Article
- Expression of senescence-associated genes in multipotent mesenchymal stromal cells during long-term cultivation at various hypoxic levels.Doklady. Biochemistry and biophysics · 2016Article
18 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
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When the cell cycle is arrested, even though growth-promoting pathways such as mTOR are still active, then cells senesce. For example, induction of either p21 or p16 arrests the cell cycle without inhibiting mTOR, which, in turn, converts p21/p16-induced arrest into senescence (geroconversion). Here we show that geroconversion is accompanied by dramatic accumulation of cyclin D1 followed by cyclin E and replicative stress. When p21 was switched off, senescent cells (despite their loss of proliferative potential) progressed through S phase, and levels of cyclins D1 and E dropped. Most cells entered mitosis and then died, either during mitotic arrest or after mitotic slippage, or underwent endoreduplication. Next, we investigated whether inhibition of mTOR would prevent accumulation of cyclins and loss of mitotic competence in p21-arrested cells. Both nutlin-3, which inhibits mTOR in these cells, and rapamycin suppressed geroconversion during p21-induced arrest, decelerated accumulation of cyclins D1 and E and decreased replicative stress. When p21 was switched off, cells successfully progressed through both S phase and mitosis. Also, senescent mouse embryonic fibroblasts (MEFs) overexpressed cyclin D1. After release from cell cycle arrest, senescent MEFs entered S phase but could not undergo mitosis and did not proliferate. We conclude that cellular senescence is characterized by futile hyper-mitogenic drive associated with mTOR-dependent mitotic incompetence.
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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.