ArticleNature cell biology2016
DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway.
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 162 papers, 3 of them syntheses that pooled it.
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The trial behind it
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Who cites it
162 citing papers in PubMed, 3 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Statins and prognosis of female breast cancer: a meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Pooled it
- Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials.European journal of clinical pharmacology · 2020Pooled it
- Impact of statin use on cancer-specific mortality and recurrence: A meta-analysis of 60 observational studies.Medicine · 2020Pooled it
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- LFPM inhibition of RING1-mediated p53Cell death and differentiation · 2026Article
- Genomic Enrichment and Functional Impact of TP53 and CYLD Alterations in Recurrent and Metastatic HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Medulloblastoma response to mevalonate pathway inhibition is independent of p53 status.Biology direct · 2026Article
- The association between cardiovascular medication use and survival in patients with advanced pancreatic adenocarcinoma.Therapeutic advances in medical oncology · 2026Article
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- Enhancement of colorectal cancer therapy through interruption of the HSF1-HSP90 axis by p53 activation or cell cycle inhibition.Cell death and differentiation · 2025Article
- The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs.Biomolecules · 2025Review
- DNAJA: emerging targets for anti-tumor therapy.Future oncology (London, England) · 2025Review
- Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.Pharmacological reports : PR · 2025Review
- The deubiquitinase inhibitor WP1130 drives nuclear aggregation and reactivation of mutant p53 for selective cancer cell targeting.The FEBS journal · 2025Article
- Molecular targets and therapies associated with poor prognosis of triple‑negative breast cancer (Review).International journal of oncology · 2025Review
- Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers.Biomolecules · 2025Review
- Analysis of p53-Independent Functions of the Mdm2-MdmX Complex Using Data-Independent Acquisition-Based Profiling.Proteomes · 2025Article
- Proteasome Inhibitor MG-132 and PKC-ι-Specific Inhibitor ICA-1S Degrade Mutant p53 and Induce Apoptosis in Ovarian Cancer Cell Lines.International journal of molecular sciences · 2025Article
- Suppression of stress granule formation is a vulnerability imposed by mutant p53.Nature communications · 2025Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member. Knockdown of DNAJA1 also induces CHIP-mediated mutp53 degradation, while its overexpression antagonizes statin-induced mutp53 degradation. Our study reveals that DNAJA1 controls the fate of misfolded mutp53, provides insights into potential strategies to deplete mutp53 through the mevalonate pathway-DNAJA1 axis, and highlights the significance of p53 status in impacting statins' efficacy on cancer therapy.
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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.