ArticleCell research2013
RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation.
Article in Cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Deciphering the role of SAMHD1 in endometrial cancer progression.Biology direct · 2024Article
- Article
- Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape.Journal of advanced research · 2023Review
- TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN.Signal transduction and targeted therapy · 2023Article
- Targeting the E3 ligase NEDD4 as a novel therapeutic strategy for IGF1 signal pathway-driven gastric cancer.Oncogene · 2023Article
- Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation.Drug design, development and therapy · 2023Article
- Review
- Emerging roles of TRIM27 in cancer and other human diseases.Frontiers in cell and developmental biology · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma.Cell death discovery · 2021Article
- TRIM27 contributes to glomerular endothelial cell injury in lupus nephritis by mediating the FoxO1 signaling pathway.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN.Molecular oncology · 2021Article
- BRCA1-associated protein 1 serves as a tumor suppressor in hepatocellular carcinoma by deubiquitinating and stabilizing PTEN.American journal of cancer research · 2021Article
- TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137.Open medicine (Warsaw, Poland) · 2021Article
- Article
- The role of ubiquitination and deubiquitination in cancer metabolism.Molecular cancer · 2020Review
- Shank-associated RH domain interactor signaling in tumorigenesis.Oncology letters · 2020Review
- Posttranslational Regulation and Conformational Plasticity of PTEN.Cold Spring Harbor perspectives in medicine · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The PTEN tumor suppressor is a lipid phosphatase that has a central role in regulating the phosphatidylinositol-3-kinase (PI3K) signal transduction cascade. Nevertheless, the mechanism by which the PTEN activity is regulated in cells needs further elucidation. Although previous studies have shown that ubiquitination of PTEN can modulate its stability and subcellular localization, the role of ubiquitination in the most critical aspect of PTEN function, its phosphatase activity, has not been fully addressed. Here, we identify a novel E3 ubiquitin ligase of PTEN, Ret finger protein (RFP), that is able to promote atypical polyubiquitinations of PTEN. These ubiquitinations do not lead to PTEN instability or relocalization, but rather significantly inhibit PTEN phosphatase activity and therefore modulate its ability to regulate the PI3K signal transduction cascade. Indeed, RFP overexpression relieves PTEN-mediated inhibitory effects on AKT activation; in contrast, RNAi-mediated knockdown of endogenous RFP enhances the ability of PTEN to suppress AKT activation. Moreover, RFP-mediated ubiquitination of PTEN inhibits PTEN-dependent activation of TRAIL expression and also suppresses its ability to induce apoptosis. Our findings demonstrate a crucial role of RFP-mediated ubiquitination in controlling PTEN activity.
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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.