ArticleCell death & disease2021
USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- USP7 promotes follicular thyroid carcinoma progression and sorafenib resistance by activating NEK2/ATG5-mediated autophagy.Histology and histopathology · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Review
- Article
- USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination.Cancer biology & therapy · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Involvement of USP7 in aggravating Kawasaki disease by promoting TGFβ2 signaling mediated endothelial-mesenchymal transition and coronary artery remodeling.International immunopharmacology · 2025Article
- Multiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC.Scientific reports · 2025Article
- The heterogeneity of genomic alterations, metastatic patterns and immune microenvironment in metastatic ovarian cancer originating from colorectal cancer.Frontiers in immunology · 2025Article
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- Inhibition of USP7 enhances CD8Acta pharmacologica Sinica · 2024Article
- Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.Bulletin of experimental biology and medicine · 2024Article
- TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination.Translational gastroenterology and hepatology · 2024Article
- Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.Frontiers in pharmacology · 2024Review
- Knocking out USP7 attenuates cardiac fibrosis and endothelial-to-mesenchymal transition by destabilizing SMAD3 in mice with heart failure with preserved ejection fraction.Theranostics · 2024Article
- Targeting the deubiquitinaseOncology reports · 2023Review
- Intricacies of TGF-β signaling in Treg and Th17 cell biology.Cellular & molecular immunology · 2023Review
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
USP7, one of the most abundant ubiquitin-specific proteases (USP), plays multifaceted roles in many cellular events, including oncogenic pathways. Accumulated studies have suggested that USP7, through modulating the MDM2/MDMX-p53 pathway, is a promising target for cancer treatment; however, little is known about the function of USP7 in p53-deficient tumors. Here we report that USP7 regulates the autoregulation of SMAD3, a key regulator of transforming growth factor β (TGFβ) signaling, that represses the cell progression of p53-deficient lung cancer. CRISPR/Cas9-mediated inactivation of USP7 in p53-deficient lung cancer H1299 line resulted in advanced cell proliferation in vitro and in xenograft tumor in vivo. Genome-wide analyses (ChIP-seq and RNA-seq) of USP7 KO H1299 cells reveal a dramatic reduction of SMAD3 autoregulation, including decreased gene expression and blunted function of associated super-enhancer (SE). Furthermore, biochemical assays show that SMAD3 is conjugated by mono-ubiquitin, which negatively regulates the DNA-binding function of SMAD3, in USP7 KO cells. In addition, cell-free and cell-based analyses further demonstrate that the deubiquitinase activity of USP7 mediates the removal of mono-ubiquitin from SMAD3 and facilitates the DNA-binding of SMAD3-SMAD4 dimer at SMAD3 locus, and thus enhance the autoregulation of SMAD3. Collectively, our study identified a novel mechanism by which USP7, through catalyzing the SMAD3 de-monoubiquitination, facilitates the positive autoregulation of SMAD3, and represses the cancer progression of p53-deficient lung cancer.
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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.