ArticleNature cell biology2016
Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.
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
160 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Inhalable Mucoadhesive Redox-Triggered Nanotherapeutics for p53-Mediated Lung Cancer Therapy and Metastasis Suppression.Advanced healthcare materials · 2026Article
- The Dynamic Alliance of p53 and Metabolism in the Tumor Microenvironment Shapes Tumor Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- TP53-META, a meta-analysis tool for comparative transcriptomics of TP53 dependency: examples from target silencing and liver fibrosis.BMC bioinformatics · 2026Article
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis.Molecular biology reports · 2026Review
- PSMC4 promotes low-grade glioma progression and predicts poor prognosis.European journal of medical research · 2026Article
- Inhibition of GPX4 induces the death of p53-mutant triple-negative breast cancer cells.Breast cancer research and treatment · 2026Article
- Dysregulation of SRSF11 in Cancer: Mechanistic Insights and Biomarker Potential for Diagnosis and Therapy.Journal of Cancer · 2026Review
- Tumor Suppressor p53 and MicroRNAs Interaction in Breast Cancer.Oncology research · 2026Review
- Proteasome stress activates YAP/TAZ through the RAP2-MAP4Ks-LATS1/2 pathway and its therapeutic implications in solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Zinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer.Cell death & disease · 2025Article
- Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor.Cell reports. Medicine · 2025Article
- K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells.Current issues in molecular biology · 2025Article
- Modulating the Immunosuppressive Tumor Microenvironment and Inhibiting Growth in Mutp53-Driven CRPC via STAT3 Pathway Blockade.International journal of biological sciences · 2025Article
- Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor.bioRxiv : the preprint server for biology · 2024Article
- Unraveling the Guardian: p53's Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies.International journal of molecular sciences · 2024Review
100 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
18 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In cancer, the tumour suppressor gene TP53 undergoes frequent missense mutations that endow mutant p53 proteins with oncogenic properties. Until now, a universal mutant p53 gain-of-function program has not been defined. By means of multi-omics: proteome, DNA interactome (chromatin immunoprecipitation followed by sequencing) and transcriptome (RNA sequencing/microarray) analyses, we identified the proteasome machinery as a common target of p53 missense mutants. The mutant p53-proteasome axis globally affects protein homeostasis, inhibiting multiple tumour-suppressive pathways, including the anti-oncogenic KSRP-microRNA pathway. In cancer cells, p53 missense mutants cooperate with Nrf2 (NFE2L2) to activate proteasome gene transcription, resulting in resistance to the proteasome inhibitor carfilzomib. Combining the mutant p53-inactivating agent APR-246 (PRIMA-1MET) with the proteasome inhibitor carfilzomib is effective in overcoming chemoresistance in triple-negative breast cancer cells, creating a therapeutic opportunity for treatment of solid tumours and metastasis with mutant p53.
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.