ArticleCell death and differentiation2015
E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Hepatitis C virus inhibits the E2F2/PI3K/AKT signaling pathway through miR-378b and leads to glycolipid metabolism disorders in the liver.Molecular biology reports · 2026Article
- Casein kinase 1δ/ε inhibition suppresses CLL proliferation through cell-intrinsic and microenvironmental mechanisms.HemaSphere · 2026Article
- Ononin Sensitizes Papillary Thyroid Carcinoma Cells to Cisplatin by Repressing DNA Damage Response via E2F2.International journal of endocrinology · 2026Article
- A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation.Genetics · 2025Article
- Article
- Cellular polyploidy in organ homeostasis and regeneration.Protein & cell · 2023Article
- E2F1 inhibits cellular senescence and promotes oxaliplatin resistance in colorectal cancer.Annals of translational medicine · 2023Article
- Targeting E2F Sensitizes Prostate Cancer Cells to Drug-Induced Replication Stress by Promoting Unscheduled CDK1 Activity.Cancers · 2022Article
- LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway.Cell proliferation · 2022Article
- E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury through Repression of Fas and FasL.International journal of molecular sciences · 2021Article
- Long non-coding RNA TMPO-AS1 promotes cell proliferation, migration, invasion and epithelial-to-mesenchymal transition in gallbladder carcinoma by regulating the microRNA-1179/E2F2 axis.Oncology letters · 2021Article
- Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice.International journal of molecular sciences · 2021Article
- Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes.Scientific reports · 2021Article
- E2F2 stimulates CCR4 expression and activates synovial fibroblast-like cells in rheumatoid arthritis.Central-European journal of immunology · 2021Article
- Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model.iScience · 2020Article
- Article
- E2F1: Cause and Consequence of DNA Replication Stress.Frontiers in molecular biosciences · 2020Review
- Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship exploited by cancer.Oncogene · 2019Article
- Cancer Genetic Network Inference Using Gaussian Graphical Models.Bioinformatics and biology insights · 2019Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53(-/-) mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy.
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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.