ArticleThe EMBO journal2018
Chk1 and 14-3-3 proteins inhibit atypical E2Fs to prevent a permanent cell cycle arrest.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells.Oncology research · 2023Article
- Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Comprehensive Profiling of Mammalian Tribbles Interactomes Implicates TRIB3 in Gene Repression.Cancers · 2021Article
- Early 2 factor (E2F) transcription factors contribute to malignant progression and have clinical prognostic value in lower-grade glioma.Bioengineered · 2021Article
- CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment.Cell reports · 2021Article
- Atypical E2Fs either Counteract or Cooperate with RB during Tumorigenesis Depending on Tissue Context.Cancers · 2021Article
- E2F7 Is a Potent Inhibitor of Liver Tumor Growth in Adult Mice.Hepatology (Baltimore, Md.) · 2021Article
- Communication between Cyclin-dependent kinase Cdc2 and the Wis1-Spc1 MAPK pathway determines mitotic timing inBiology open · 2020Article
- Intrinsic ATR signaling shapes DNA end resection and suppresses toxic DNA-PKcs signaling.NAR cancer · 2020Article
- Small Nuclear Ribonucleoprotein Polypeptide N Accelerates Malignant Progression and Poor Prognosis in Colorectal Cancer Transcriptionally Regulated by E2F8.Frontiers in oncology · 2020Article
- Article
- Cyclin F-dependent degradation of E2F7 is critical for DNA repair and G2-phase progression.The EMBO journal · 2019Article
- The broken cycle: E2F dysfunction in cancer.Nature reviews. Cancer · 2019Review
- Impact of Replication Stress in Human Papillomavirus Pathogenesis.Journal of virology · 2019Review
- Identification of the Different Roles and Potential Mechanisms of T Isoforms in the Tumor Recurrence and Cell Cycle of Chordomas.OncoTargets and therapy · 2019Article
- Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells.Nucleic acids research · 2018Article
- The live cell DNA stain SiR-Hoechst induces DNA damage responses and impairs cell cycle progression.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The atypical E2Fs, E2F7 and E2F8, act as potent transcriptional repressors of DNA replication genes providing them with the ability to induce a permanent S-phase arrest and suppress tumorigenesis. Surprisingly in human cancer, transcript levels of atypical E2Fs are frequently elevated in proliferating cancer cells, suggesting that the tumor suppressor functions of atypical E2Fs might be inhibited through unknown post-translational mechanisms. Here, we show that atypical E2Fs can be directly phosphorylated by checkpoint kinase 1 (Chk1) to prevent a permanent cell cycle arrest. We found that 14-3-3 protein isoforms interact with both E2Fs in a Chk1-dependent manner. Strikingly, Chk1 phosphorylation and 14-3-3-binding did not relocate or degrade atypical E2Fs, but instead, 14-3-3 is recruited to E2F7/8 target gene promoters to possibly interfere with transcription. We observed that high levels of 14-3-3 strongly correlate with upregulated transcription of atypical E2F target genes in human cancer. Thus, we reveal that Chk1 and 14-3-3 proteins cooperate to inactivate the transcriptional repressor functions of atypical E2Fs. This mechanism might be of particular importance to cancer cells, since they are exposed frequently to DNA-damaging therapeutic reagents.
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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.