ArticleJournal of cell science2009
Impairment of ubiquitylation by mutation in Drosophila E1 promotes both cell-autonomous and non-cell-autonomous Ras-ERK activation in vivo.
Article in Journal of cell science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Knockdown of PR-DUB subunit calypso in the developing Drosophila eye and wing results in mis-patterned tissues with altered size and shape.G3 (Bethesda, Md.) · 2025Article
- Review
- Protein networking: nicotinic acetylcholine receptors and their protein-protein-associations.Molecular and cellular biochemistry · 2024Review
- Rabex-5 E3 and Rab5 GEF domains differ in their regulation of Ras, Notch, and PI3K signaling in Drosophila wing development.PloS one · 2024Article
- Characterization of Ras Y4H mutants inmicroPublication biology · 2024Article
- Lysines K117 and K147 play conserved roles in Ras activation from Drosophila to mammals.G3 (Bethesda, Md.) · 2023Article
- WASH activation controls endosomal recycling and EGFR and Hippo signaling during tumor-suppressive cell competition.Nature communications · 2022Article
- Somatic Mutations inThe New England journal of medicine · 2020Article
- A conserved, N-terminal tyrosine signal directs Ras for inhibition by Rabex-5.PLoS genetics · 2020Article
- Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos.Scientific reports · 2019Article
- RAS: Striking at the Core of the Oncogenic Circuitry.Frontiers in oncology · 2019Review
- When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling.Cell communication and signaling : CCS · 2013Review
- Dpp-induced Egfr signaling triggers postembryonic wing development in Drosophila.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.PloS one · 2013Article
- CRL Ubiquitin Ligases and DNA Damage Response.Frontiers in oncology · 2012Article
- Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors.Science signaling · 2011Article
- Ubiquitin on ras: warden or partner in crime?Science signaling · 2011Review
- Ras, an actor on many stages: posttranslational modifications, localization, and site-specified events.Genes & cancer · 2011Article
- Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.Current biology : CB · 2010Article
- Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.Current biology : CB · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ras signaling can promote proliferation, cell survival and differentiation. Mutations in components of the Ras pathway are found in many solid tumors and are associated with developmental disorders. We demonstrate here that Drosophila tissues containing hypomorphic mutations in E1, the most upstream enzyme in the ubiquitin pathway, display cell-autonomous upregulation of Ras-ERK activity and Ras-dependent ectopic proliferation. Ubiquitylation is widely accepted to regulate receptor tyrosine kinase (RTK) endocytosis upstream of Ras. However, although the ectopic proliferation of E1 hypomorphs is dramatically suppressed by removing one copy of Ras, removal of the more upstream components Egfr, Grb2 or sos shows no suppression. Thus, decreased ubiquitylation may lead to growth-relevant Ras-ERK activation by failing to regulate a step downstream of RTK endocytosis. We further demonstrate that Drosophila Ras is ubiquitylated. Our findings suggest that Ras ubiquitylation restricts growth and proliferation in vivo. We also report our intriguing observation that complete inactivation of E1 causes non-autonomous activation of Ras-ERK in adjacent tissue, mimicking oncogenic Ras overexpression. We demonstrate that maintaining sufficient E1 function is required both cell autonomously and non-cell autonomously to prevent inappropriate Ras-ERK-dependent growth and proliferation in vivo and may implicate loss of Ras ubiquitylation in developmental disorders and cancer.
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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.