ArticleCell research2018
Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- Deubiquitinase USP43 exacerbates myocardial ischemia-reperfusion injury by stabilizing ASK1 and activating the JNK/P38 MAPK pathway.Basic research in cardiology · 2026Article
- USP43 Inhibits Intestinal Inflammation via TRAF4-mediated NF-κB Signaling.Inflammation · 2026Article
- Glucocorticoids elevate clear cell renal cell carcinoma sensitivity to HIF-2α inhibitors by suppressing H4K12 lactylation.Signal transduction and targeted therapy · 2026Article
- The E3 ubiquitin ligase RNF180 modulates the EGFR/PI3K/AKT pathway to reduce cisplatin resistance in non-small cell lung cancer.Scientific reports · 2026Article
- The role of deubiquitinase USP33 in colorectal cancer tumorigenesis and its potential as a therapeutic target predictor.Discover oncology · 2026Review
- Transcriptome-wide identification of glycoRNAs by Clier-seq pipeline.Science China. Life sciences · 2026Article
- Kuwanon A Targeted YWHAB in Hepatocellular Carcinoma Cells to Inhibit the Raf/MEK/ERK Signaling Pathway.Cells · 2025Article
- YY1-induced USP43 drives ferroptosis suppression by FASN stabilization and subsequent activation of SLC7A11 in ovarian cancer.Cell death & disease · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Review
- DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis.Biochemical genetics · 2024Article
- USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer.Cell death & disease · 2024Article
- Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation.Oncology research · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperactivation of EGFR/PI3K/AKT is a prominent feature of various human cancers. Thus, understanding how this molecular cascade is balanced is of great importance. We report here that the ubiquitin-specific protease USP43 is physically associated with the chromatin remodeling NuRD complex and catalyzes H2BK120 deubiquitination. Functionally this coordinates the NuRD complex to repress a cohort of genes, including EGFR, which are critically involved in cell proliferation and carcinogenesis. We show that USP43 strongly suppresses the growth and metastasis of breast cancer in vivo. Interestingly, USP43 also exists in the cytoplasm, where it is phosphorylated by AKT, enabling its binding to the 14-3-3β/ε heterodimer and sequestration in the cytoplasm. Significantly, hyperactivation of EGFR/PI3K/AKT in breast cancer is associated with the cytoplasmic retention of USP43 and thus, the inhibition of its transcriptional regulatory function. Moreover, cancer-associated mutations of USP43 affect its subcellular localization and/or epigenetic regulatory functions. Nuclear USP43 is significantly reduced in breast carcinomas and is associated with EGFR accumulation and AKT hyperactivation. A low level of nuclear USP43 correlates with higher histologic grades and poor prognosis. Our study identifies USP43 to be an H2BK120 deubiquitinase and a potential tumor suppressor and reveals a reciprocally inhibitory loop between USP43 and EGFR/PI3K/AKT, whose imbalance drives breast carcinogenesis.
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