ArticleProceedings of the National Academy of Sciences of the United States of America2005
Ras activity regulates cyclin E degradation by the Fbw7 pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Review
- The origin of bladder cancer from mucosal field effects.iScience · 2022Article
- KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis.Cell death & disease · 2022Article
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.Cancers · 2021Review
- Ubiquitin signaling in cell cycle control and tumorigenesis.Cell death and differentiation · 2021Review
- Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.Cancers · 2020Review
- Article
- FBXW7: a critical tumor suppressor of human cancers.Molecular cancer · 2018Review
- F-box proteins involved in cancer-associated drug resistance.Oncology letters · 2018Review
- PIN1 in breast development and cancer: a clinical perspective.Cell death and differentiation · 2017Review
- Article
- A new mitochondrial pool of cyclin E, regulated by Drp1, is linked to cell-density-dependent cell proliferation.Journal of cell science · 2015Article
- Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients.BMC cancer · 2015Article
- ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer.Cell research · 2015Article
- Indole-3-carbinol (I3C) increases apoptosis, represses growth of cancer cells, and enhances adenovirus-mediated oncolysis.Cancer biology & therapy · 2014Article
- Prolyl isomerase Pin1 in cancer.Cell research · 2014Review
- Chromosome instability underlies hematopoietic stem cell dysfunction and lymphoid neoplasia associated with impaired Fbw7-mediated cyclin E regulation.Molecular and cellular biology · 2014Article
- SCF(FBXW7α) modulates the intra-S-phase DNA-damage checkpoint by regulating Polo like kinase-1 stability.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The Skp1-Cullin1 F-box protein-Fbw7 ubiquitin ligase regulates phosphorylation-dependent cyclin E degradation, and disruption of this pathway is associated with genetic instability and tumorigenesis. Fbw7 is a human tumor suppressor that is targeted for mutation in primary cancers. However, mechanisms other than mutation of Fbw7 may also disrupt cyclin E proteolysis in cancers. We show that oncogenic Ha-Ras activity regulates cyclin E degradation by the Fbw7 pathway. Activated Ras impairs Fbw7-driven cyclin E degradation, and, conversely, inhibition of normal Ras activity decreases cyclin E abundance. Moreover, activation of the mitogen-activated protein kinase pathway is the essential Ras function that inhibits cyclin E turnover, and activated Ha-Ras expression inhibits both the binding of cyclin E to Fbw7 and cyclin E ubiquitination. Last, we found that oncogenic Ras activity potentiates cyclin E-induced genetic instability but only when cyclin E is susceptible to degradation by Fbw7. Thus, we conclude that Ras activity regulates Fbw7-mediated cyclin E proteolysis and suggest that impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis.
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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.