ArticleCell death & disease2022
USP7 regulates the ERK1/2 signaling pathway through deubiquitinating Raf-1 in lung adenocarcinoma.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Ubiquitin-specific peptidases in lymphoma: a path to novel therapeutics.Frontiers in pharmacology · 2024Pooled it
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- USP37 facilitates hepatocellular carcinoma progression by deubiquitinating RAF1 and activating ERK1/2 signaling.Functional & integrative genomics · 2026Article
- Article
- USP7 at PML Nuclear Bodies: A Protein Interaction Network Perspective.International journal of molecular sciences · 2026Article
- Ubiquitin-Specific Protease 45 Inhibits Lung Adenocarcinoma Ferroptosis by Regulating Ubiquitination and Stability of Glutathione Peroxidase 4.Cancer medicine · 2026Article
- GPR35 protects against reperfusion injury in ischemic stroke by binding with the CR2 domain of Raf1.Journal of neuroinflammation · 2026Article
- Deubiquitination of ETV4 by USP7 Promotes NSCLC Tumorigenesis via MAPK7 Activation.Human mutation · 2026Article
- Review
- Role of ubiquitin‑proteasome system in preeclampsia (Review).Molecular medicine reports · 2026Review
- Methyl jasmonate elicitation enhances photoprotective and anti-inflammatory properties in Lavandula angustifolia cell suspension cultures.Scientific reports · 2025Article
- MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways.NPJ precision oncology · 2025Article
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- Targeting Ubiquitin-Specific Protease 7 with Novel 5-Amino-Pyrazole Inhibitors: Design, Synthesis, and Biological Evaluation.ChemMedChem · 2025Article
- Exosomal circ-0100519 promotes breast cancer progression via inducing M2 macrophage polarisation by USP7/NRF2 axis.Clinical and translational medicine · 2024Article
- Article
- The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis.Journal of experimental & clinical cancer research : CR · 2024Article
- The use of matrine to inhibit osteosarcoma cell proliferation via the regulation of the MAPK/ERK signaling pathway.Frontiers in oncology · 2024Article
- SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation.Clinical and translational medicine · 2024Article
- Synergistic effect of YOD1 and USP21 on the Hippo signaling pathway.Cancer cell international · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitin-specific protease 7 (USP7) is one of the deubiquitinating enzymes (DUBs) in the ubiquitin-specific protease (USP) family. It is a key regulator of numerous cellular functions including immune response, cell cycle, DNA damage and repair, epigenetics, and several signaling pathways. USP7 acts by removing ubiquitin from the substrate proteins. USP7 also binds to a specific binding motif of substrate proteins having the [P/A/E]-X-X-S or K-X-X-X-K protein sequences. To date, numerous substrate proteins of USP7 have been identified, but no studies have been conducted using the binding motif that USP7 binds. In the current study, we analyzed putative substrate proteins of USP7 through the [P/A/E]-X-X-S and K-X-X-X-K binding motifs using bioinformatics tools, and confirmed that Raf-1 is one of the substrates for USP7. USP7 binds to the Pro-Val-Asp-Ser (PVDS) motif of the conserved region 2 (CR2) which contains phosphorylation sites of Raf-1 and decreased M1-, K6-, K11-, K27-, K33-, and K48-linked polyubiquitination of Raf-1. We further identified that the DUB activity of USP7 decreases the threonine phosphorylation level of Raf-1 and inhibits signaling transduction through Raf activation. This regulatory mechanism inhibits the activation of the ERK1/2 signaling pathway, thereby inhibiting the G2/M transition and the cell proliferation of lung adenocarcinoma cells. In summary, our results indicate that USP7 deubiquitinates Raf-1 and is a new regulator of the ERK1/2 signaling pathway in lung adenocarcinoma.
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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.