ArticleThe Journal of clinical investigation2023
The ubiquitin ligase TRIM21 regulates mutant p53 accumulation and gain of function in cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 59 citations in OpenAlex.
- YME1L1 degradation by TRIM21 inhibits bladder cancer proliferation, metastasis, and mitochondrial function.Oncogene · 2026Article
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- Ubiquitination and NOncology letters · 2026Review
- Resveratrol derivative restores macrophage cholesterol homeostasis via stabilizing xanthine oxidoreductase in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Fuzuloparib enhances radiosensitivity of gain-of-function mutant p53 R273H NSCLC by promoting SLC7A11/GSH/GPX4 axis mediated ferroptosis.NPJ precision oncology · 2026Article
- Fundamentals and emerging frontiers in p53-targeted drug development.Biochemistry and biophysics reports · 2026Review
- RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability and inhibiting H3K18 lactylation.Cell death & disease · 2026Article
- Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer.Communications biology · 2026Article
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- TRIM21-Mediated ubiquitination of FBL suppresses PI3K/AKT signaling and tumor progression in clear cell renal cell carcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Induction of ferroptosis in prostate cancer by CCDC7Cell death and differentiation · 2026Article
- Functional characterization of CASP, aiScience · 2026Article
- Mutant p53 Regulates Pyruvate Dehydrogenase Kinase 1 (PDK1) to Promote Proliferation and Migration in Breast Cancer.Cancer science · 2026Article
- The p53 R181C mutation accumulates through impaired deacetylation by Sirt1 and facilitates tumor development.Communications biology · 2026Article
- TRIM21 and OTUD6A orchestrate AKT K27-linked atypical ubiquitination to modulate cancer chemoresistance.Nature structural & molecular biology · 2026Article
- UBE2W promotes pancreatic cancer progression through regulating K63-linked ubiquitination of p53.American journal of cancer research · 2026Article
- TRIM21 suppresses uterine corpus endometrial carcinoma progression by promoting K48 -linked ubiquitination and degradation of SOAT1.Frontiers in immunology · 2026Article
- TAF1 acetyltransferase promotes colorectal carcinoma metastasis by catalyzing β-hydroxybutyrylation of KCTD9.Oncogene · 2026Article
- Ubiquitin-conjugating enzyme E2S serves as a prognostic marker for skin cutaneous melanoma.Translational cancer research · 2025Article
- Targeting AQP5-mediated arginine deprivation in gastric cancer stem cells restores NK cell anti-tumor immunity.Cell reports. Medicine · 2025Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The tumor suppressor TP53 is the most frequently mutated gene in human cancers. Mutant p53 (mutp53) proteins often accumulate to very high levels in human cancers to promote cancer progression through the gain-of-function (GOF) mechanism. Currently, the mechanism underlying mutp53 accumulation and GOF is incompletely understood. Here, we identified TRIM21 as a critical E3 ubiquitin ligase of mutp53 by screening for specific mutp53-interacting proteins. TRIM21 directly interacted with mutp53 but not WT p53, resulting in ubiquitination and degradation of mutp53 to suppress mutp53 GOF in tumorigenesis. TRIM21 deficiency in cancer cells promoted mutp53 accumulation and GOF in tumorigenesis. Compared with p53R172H knockin mice, which displayed mutp53 accumulation specifically in tumors but not normal tissues, TRIM21 deletion in p53R172H knockin mice resulted in mutp53 accumulation in normal tissues, an earlier tumor onset, and a shortened life span of mice. Furthermore, TRIM21 was frequently downregulated in some human cancers, including colorectal and breast cancers, and low TRIM21 expression was associated with poor prognosis in patients with cancers carrying mutp53. Our results revealed a critical mechanism underlying mutp53 accumulation in cancers and also uncovered an important tumor-suppressive function of TRIM21 and its mechanism in cancers carrying mutp53.
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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.