ArticleCurrent biology : CB2010
Rabex-5 ubiquitin ligase activity restricts Ras signaling to establish pathway homeostasis in Drosophila.
Article in Current biology : CB, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- miR-34 regulates stress-induced depression-like state through theResearch square · 2026Article
- 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
- Characterization of Ras Y4H mutants inmicroPublication biology · 2024Article
- Rabex-5 E3 and Rab5 GEF domains differ in their regulation of Ras, Notch, and PI3K signaling in Drosophila wing development.PloS one · 2024Article
- Lysines K117 and K147 play conserved roles in Ras activation from Drosophila to mammals.G3 (Bethesda, Md.) · 2023Article
- The Four Homeostasis Knights: In Balance upon Post-Translational Modifications.International journal of molecular sciences · 2022Review
- AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.Nature communications · 2022Article
- Post-translational modification of RAS proteins.Current opinion in structural biology · 2021Review
- Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators.Acta pharmaceutica Sinica. B · 2021Review
- DAB2IP modulates primary cilia formation associated with renal tumorigenesis.Neoplasia (New York, N.Y.) · 2021Article
- Capturing the transcription factor interactome in response to sub-lethal insecticide exposure.Current research in insect science · 2021Article
- Divergent Mechanisms Activating RAS and Small GTPases Through Post-translational Modification.Frontiers in molecular biosciences · 2021Review
- A conserved, N-terminal tyrosine signal directs Ras for inhibition by Rabex-5.PLoS genetics · 2020Article
- Therapeutic targeting of RAS: New hope for drugging the "undruggable".Biochimica et biophysica acta. Molecular cell research · 2020Review
- Biology, pathology, and therapeutic targeting of RAS.Advances in cancer research · 2020Review
- Regulation of large and small G proteins by ubiquitination.The Journal of biological chemistry · 2019Review
- Recycling Endosomes in Mature Epithelia Restrain Tumorigenic Signaling.Cancer research · 2019Article
- LZTR1 is a regulator of RAS ubiquitination and signaling.Science (New York, N.Y.) · 2018Article
- Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.Science (New York, N.Y.) · 2018Article
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5 authors at 1 institution in 1 country.
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Abstract
The Ras signaling pathway allows cells to translate external cues into diverse biological responses. Depending on context and the threshold reached, Ras signaling can promote growth, proliferation, differentiation, or cell survival. Failure to maintain precise control of Ras can have adverse physiological consequences. Indeed, excess Ras signaling disrupts developmental patterning and causes developmental disorders [1, 2], and in mature tissues, it can lead to cancer [3-5]. We identify Rabex-5 as a new component of Ras signaling crucial for achieving proper pathway outputs in multiple contexts in vivo. We show that Drosophila Rabex-5 restricts Ras signaling to establish organism size, wing vein pattern, and eye versus antennal fate. Rabex-5 has both Rab5 guanine nucleotide exchange factor (GEF) activity that regulates endocytic trafficking [6] and ubiquitin ligase activity [7, 8]. Surprisingly, overexpression studies demonstrate that Rabex-5 ubiquitin ligase activity, not its Rab5 GEF activity, is required to restrict wing vein specification and to suppress the eye phenotypes of oncogenic Ras expression. Furthermore, genetic interaction experiments indicate that Rabex-5 acts at the step of Ras, and tissue culture studies show that Rabex-5 promotes Ras ubiquitination. Together, these findings reveal a new mechanism for attenuating Ras signaling in vivo and suggest an important role for Rabex-5-mediated Ras ubiquitination in pathway homeostasis.
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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.