ArticleThe EMBO journal2024
K128 ubiquitination constrains RAS activity by expanding its binding interface with GAP proteins.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- The Role of KRAS in Non-Small Cell Lung Cancer: From Molecular Background to Precision Medicine.International journal of molecular sciences · 2026Review
- Non-canonical and constitutive activation of small GTPases: more than an exception to the rule?The Biochemical journal · 2026Review
- SYVN1-provoked RASA1 ubiquitination promotes pulmonary inflammation in chronic obstructive pulmonary disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- [miR-143-3p alleviates neuropathic pain in mice with spared nerve injury by targeting the KRAS/RalA pathway and inhibiting astrocyte activation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The structural basis of RanGAP1 regulation and catalysis in nuclear transport.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- From metabolic substrate to epigenetic regulation: roles and mechanisms of lactylation in brain health and disease.Frontiers in molecular neuroscience · 2026Review
- Proteomic Perspectives on KRAS-Driven Cancers and Emerging Therapeutic Approaches.Current oncology (Toronto, Ont.) · 2025Review
- Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- The differential interactomes of the KRAS splice variants identify BIRC6 as a ubiquitin ligase for KRAS4A.Cell reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
The RAS pathway is among the most frequently activated signaling nodes in cancer. However, the mechanisms that alter RAS activity in human pathologies are not entirely understood. The most prevalent post-translational modification within the GTPase core domain of NRAS and KRAS is ubiquitination at lysine 128 (K128), which is significantly decreased in cancer samples compared to normal tissue. Here, we found that K128 ubiquitination creates an additional binding interface for RAS GTPase-activating proteins (GAPs), NF1 and RASA1, thus increasing RAS binding to GAP proteins and promoting GAP-mediated GTP hydrolysis. Stimulation of cultured cancer cells with growth factors or cytokines transiently induces K128 ubiquitination and restricts the extent of wild-type RAS activation in a GAP-dependent manner. In KRAS mutant cells, K128 ubiquitination limits tumor growth by restricting RAL/ TBK1 signaling and negatively regulating the autocrine circuit induced by mutant KRAS. Reduction of K128 ubiquitination activates both wild-type and mutant RAS signaling and elicits a senescence-associated secretory phenotype, promoting RAS-driven pancreatic tumorigenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.