ArticleCancer research2014
Cancer-derived mutations in KEAP1 impair NRF2 degradation but not ubiquitination.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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
83 citing papers in PubMed, 140 citations in OpenAlex.
- Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth.Cancer discovery · 2026Article
- Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer.bioRxiv : the preprint server for biology · 2026Article
- The lncRNA DAMER selectively guides mNature cell biology · 2026Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Review
- Redox phenotype confers T cell-exclusion microenvironment and resistance to immunotherapy by suppressingFrontiers in oncology · 2025Article
- Understanding serine and glycine metabolism in cancer: a path towards precision medicine to improve patient's outcomes.Discover oncology · 2024Review
- Engineered Cas9 variants bypass Keap1-mediated degradation in human cells and enhance epigenome editing efficiency.Nucleic acids research · 2024Article
- Predicting drug response through tumor deconvolution by cancer cell lines.Patterns (New York, N.Y.) · 2024Article
- Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024Article
- Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells.Redox biology · 2024Article
- Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.Cell reports · 2024Article
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- Nrf2 in human cancers: biological significance and therapeutic potential.American journal of cancer research · 2024Review
- Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2.Science signaling · 2023Article
- KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance.Cell reports · 2023Article
- Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3.International journal of molecular sciences · 2023Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
NRF2 is a transcription factor that mediates stress responses. Oncogenic mutations in NRF2 localize to one of its two binding interfaces with KEAP1, an E3 ubiquitin ligase that promotes proteasome-dependent degradation of NRF2. Somatic mutations in KEAP1 occur commonly in human cancer, where KEAP1 may function as a tumor suppressor. These mutations distribute throughout the KEAP1 protein but little is known about their functional impact. In this study, we characterized 18 KEAP1 mutations defined in a lung squamous cell carcinoma tumor set. Four mutations behaved as wild-type KEAP1, thus are likely passenger events. R554Q, W544C, N469fs, P318fs, and G333C mutations attenuated binding and suppression of NRF2 activity. The remaining mutations exhibited hypomorphic suppression of NRF2, binding both NRF2 and CUL3. Proteomic analysis revealed that the R320Q, R470C, G423V, D422N, G186R, S243C, and V155F mutations augmented the binding of KEAP1 and NRF2. Intriguingly, these "super-binder" mutants exhibited reduced degradation of NRF2. Cell-based and in vitro biochemical analyses demonstrated that despite its inability to suppress NRF2 activity, the R320Q "superbinder" mutant maintained the ability to ubiquitinate NRF2. These data strengthen the genetic interactions between KEAP1 and NRF2 in cancer and provide new insight into KEAP1 mechanics.
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.