ArticleAging cell2017
Cooperation between p21 and Akt is required for p53-dependent cellular senescence.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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.
The trial behind it
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Who cites it
62 citing papers in PubMed, 107 citations in OpenAlex.
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- Transdermal delivery of salvianolic acid B using thermosensitive hydrogel for the treatment of skin photoaging.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Transcriptomic profile of RNA pseudouridine modification as a biomarker for cellular senescence associated with survival outcomes in colorectal cancer.BMC biology · 2025Article
- A Multidimensional Study Integrating Traditional Chinese Medicine and Network Pharmacology: Exploring the Skin Repair and Anti-Aging Effects of a Specific Combination of Five-Colored Plants.Clinical, cosmetic and investigational dermatology · 2025Article
- The potential of flavonoids to mitigate cellular senescence in cardiovascular disease.Biogerontology · 2024Review
- Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.Acta pharmacologica Sinica · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Inhibition of endogenous hydrogen sulfide production reduces activation of hepatic stellate cells via the induction of cellular senescence.Cell cycle (Georgetown, Tex.) · 2024Article
- New Insights into Chemoresistance Mediated by Mdm2 Inhibitors: The Benefits of Targeted Therapy over Common Cytostatics.Biomedicines · 2024Article
- Long non-coding RNA generated from CDKN1A gene by alternative polyadenylation regulates p21 expression during DNA damage response.Nucleic acids research · 2023Article
- Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells.Communications biology · 2023Article
- Cellular Senescence: A Troy Horse in Pulmonary Fibrosis.International journal of molecular sciences · 2023Review
- UnripePreventive nutrition and food science · 2023Article
- Breast Cancer Mutations HER2V777L and PIK3CAH1047R Activate the p21-CDK4/6-Cyclin D1 Axis to Drive Tumorigenesis and Drug Resistance.Cancer research · 2023Article
- The Role of the Kynurenine Pathway in the Pathophysiology of Frailty, Sarcopenia, and Osteoporosis.Nutrients · 2023Review
- Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics.Tissue barriers · 2023Article
- Gut Microbiota is Associated with Aging-Related Processes of a Small Mammal Species under High-Density Crowding Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- 11-Cl-BBQ, a select modulator of AhR-regulated transcription, suppresses lung cancer cell growth via activation of p53 and p27The FEBS journal · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence has been implicated in normal aging, tissue homeostasis, and tumor suppression. Although p53 has been shown to be a central mediator of cellular senescence, the signaling pathway by which it induces senescence remains incompletely understood. In this study, we have shown that both Akt and p21 are required to induce cellular senescence in response to p53 expression. In a p53-induced senescence model, we found that Akt activation was essential for inducing a cellular senescence phenotype. Surprisingly, Akt inhibition did not abolish p53-induced cell cycle arrest, but it suppressed the increase in intracellular reactive oxygen species (ROS) levels. The results of the cell cycle and morphological analysis suggest that p53 induced quiescence, not senescence, following Akt inhibition. Conversely, the inhibition of p21 induction abolished cell cycle arrest but did not affect the p53-induced increase in ROS levels. Additionally, p21 and Akt separately controlled cell cycle arrest and ROS levels, respectively, during H-Ras-induced senescence in human normal fibroblasts. The mechanistic analysis revealed that Akt increased ROS levels through NOX4 induction, and increased Akt-dependent NF-κB binding to the NOX4 promoter is responsible for NOX4 induction upon p53 expression. We further showed that Akt activation upon p53 expression is mediated by mammalian target of rapamycin complex 2. In addition, p53-mediated IL6 and IL8 induction was abrogated by Akt inhibition, suggesting that Akt activation is also required for the senescence-associated secretory phenotype. Collectively, these results suggest that p53 simultaneously controls multiple pathways to induce cellular senescence through p21 and Akt.
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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.