ArticleScientific reports2015
Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon.Communications biology · 2023Pooled it
- Threonine 348 regulates the subcellular localization of PTEN.FEBS open bio · 2026Article
- Elucidating PTEN conformational dynamics and phosphatase regulation via integrative modeling and mutation prediction.Structure (London, England : 1993) · 2025Article
- Phenotypic rescue via mTOR inhibition in neuron-specific Pten knockout mice reveals AKT and mTORC1-site specific changes.Molecular psychiatry · 2025Article
- Genetically encoded biosensor for fluorescence lifetime imaging of PTEN dynamics in the intact brain.Nature methods · 2025Article
- Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis.iScience · 2024Article
- Semisynthetic Approach to the Analysis of Tumor Suppressor PTEN Ubiquitination.Journal of the American Chemical Society · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- Structural and Dynamic Effects of PTEN C-Terminal Tail Phosphorylation.Journal of chemical information and modeling · 2022Article
- Shape shifting: The multiple conformational substates of the PTEN N-terminal PIPProtein science : a publication of the Protein Society · 2022Article
- Immunofluorescence Detection of Plasma Membranous PTEN in Cultured Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- The Loss of Nuclear PTEN Increases Tumorigenesis in a Preclinical Mouse Model for Hepatocellular Carcinoma.iScience · 2020Article
- Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.Cells · 2020Article
- Review
- Site-Specific Protein Labeling with N-Hydroxysuccinimide-Esters and the Analysis of Ubiquitin Ligase Mechanisms.Journal of the American Chemical Society · 2018Article
- Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility.The Journal of biological chemistry · 2018Article
- PTEN Physically Interacts with and Regulates E2F1-mediated Transcription in Lung Cancer.Cell cycle (Georgetown, Tex.) · 2018Article
- Article
- Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor suppressor PTEN mainly functions at two subcellular locations, the plasma membrane and the nucleus. At the plasma membrane, PTEN dephosphorylates the tumorigenic second messenger PIP3, which drives cell proliferation and migration. In the nucleus, PTEN controls DNA repair and genome stability independently of PIP3. Whereas the concept that a conformational change regulates protein function through post-translational modifications has been well established in biology, it is unknown whether a conformational change simultaneously controls dual subcellular localizations of proteins. Here, we discovered that opening the conformation of PTEN is the crucial upstream event that determines its key dual localizations of this crucial tumor suppressor. We identify a critical conformational switch that regulates PTEN's localization. Most PTEN molecules are held in the cytosol in a closed conformation by intramolecular interactions between the C-terminal tail and core region. Dephosphorylation of the tail opens the conformation and exposes the membrane-binding regulatory interface in the core region, recruiting PTEN to the membrane. Moreover, a lysine at residue 13 is also exposed and when ubiquitinated, transports PTEN to the nucleus. Thus, opening the conformation of PTEN is a key mechanism that enhances its dual localization and enzymatic activity, providing a potential therapeutic strategy in cancer treatments.
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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.