ArticleCell death and differentiation2013
MEK drives cyclin D1 hyperelevation during geroconversion.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 89 citations in OpenAlex.
- Cyclin D1 regulates the hepatic response to feeding: Evidence for non-cell cycle roles in the liver.bioRxiv : the preprint server for biology · 2026Article
- 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
- Comprehensive bulk and single-cell RNA sequencing uncovers senescence-associated biomarkers in therapeutic mesenchymal stem cells.Scientific reports · 2025Article
- Determination of ADP/ATP translocase isoform ratios in malignancy and cellular senescence.Molecular oncology · 2025Article
- HIV-Tat upregulates the expression of senescence biomarkers in CD4Frontiers in immunology · 2025Article
- SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina.npj aging · 2024Article
- Mitogen signaling strength and duration can control cell cycle decisions.Science advances · 2024Review
- AKR1B10 inhibits the proliferation and metastasis of hepatocellular carcinoma cells by regulating the PI3K/AKT pathway.Oncology letters · 2024Article
- Biological Effects of "Inflammageing" on Human Oral Cells: Insights into a Potential Confounder of Age-Related Diseases.International journal of molecular sciences · 2023Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- Increased cell senescence in human metabolic disorders.The Journal of clinical investigation · 2023Review
- Article
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- Cell senescence, rapamycin and hyperfunction theory of aging.Cell cycle (Georgetown, Tex.) · 2022Review
- CAMSAP3 depletion induces lung cancer cell senescence-associated phenotypes through extracellular signal-regulated kinase inactivation.Cancer medicine · 2021Article
- Outcomes of Deferoxamine Action on HInternational journal of molecular sciences · 2021Article
- Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Functional Determinants of Cell Cycle Plasticity and Sensitivity to CDK4/6 Inhibition.Cancer research · 2021Article
- From causes of aging to death from COVID-19.Aging · 2020Review
11 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When the cell cycle becomes arrested, MTOR (mechanistic Target of Rapamycin) converts reversible arrest into senescence (geroconversion). Hyperexpression of cyclin D1 is a universal marker of senescence along with hypertrophy, beta-Gal staining and loss of replicative/regenerative potential (RP), namely, the ability to restart proliferation when the cell cycle is released. Inhibition of MTOR decelerates geroconversion, although only partially decreases cyclin D1. Here we show that in p21- and p16-induced senescence, inhibitors of mitogen-activated/extracellular signal-regulated kinase (MEK) (U0126, PD184352 and siRNA) completely prevented cyclin D1 accumulation, making it undetectable. We also used MEL10 cells in which MEK inhibitors do not inhibit MTOR. In such cells, U0126 by itself induced senescence that was remarkably cyclin D1 negative. In contrast, inhibition of cyclin-dependent kinase (CDK) 4/6 by PD0332991 caused cyclin D1-positive senescence in MEL10 cells. Both types of senescence were suppressed by rapamycin, converting it into reversible arrest. We confirmed that the inhibitor of CDK4/6 caused cyclin D1 positive senescence in normal RPE cells, whereas U0126 prevented cyclin D1 expression. Elimination of cyclin D1 by siRNA did not prevent other markers of senescence that are consistent with the lack of its effect on MTOR. Our data confirmed that a mere inhibition of the cell cycle was sufficient to cause senescence, providing MTOR was active, and inhibition of MEK partially inhibited MTOR in a cell-type-dependent manner. Second, hallmarks of senescence may be dissociated, and hyperelevated cyclin D1, a marker of hyperactivation of senescent cells, did not necessarily determine other markers of senescence. Third, inhibition of MEK was sufficient to eliminate cyclin D1, regardless of MTOR.
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