ArticleEMBO reports2020
The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
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Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 66 citations in OpenAlex.
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- Distinct palmitoylation of Foxp3 regulates the function of regulatory T cells via palmitoyltransferases.Cellular & molecular immunology · 2024Article
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- CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis.Journal of molecular cell biology · 2024Article
- Mechanism of miR-98-5p in gastric cancer cell proliferation, migration, and invasion through the USP44/CTCFL axis.Toxicology research · 2024Article
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
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Authors and funding
33 authors at 10 institutions in 2 countries.
Jing Yang *Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ping Wei *Department of Otolaryngology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Joseph BarbiDepartment of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.ORCID 0000-0002-5632-0885
Qianru HuangShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Evan YangImmunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yakun BaiHenan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
Jia NieShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yanhang GaoDepartment of Hepatology, First Hospital, Jilin University, Changchun, Jilin, China.
Jinhui TaoImmunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ying LuShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chichu XieDivision of Rheumatology, Department of Medicine, Penn State Hershey College of Medicine, Hershey, PA, USA.
Xiaoxia HouDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiazi RenKey Laboratory of Molecular Virology & Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Xingmei WuENT Department, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.
Jian MengShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ying ZhangDepartment of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Juan FuImmunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Wei KouDepartment of Otolaryngology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Yayi GaoShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Zuojia ChenShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Rui LiangShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Andy TsunShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Dan LiShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Wenzhi GuoHenan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
Shuijun ZhangHenan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
Song-Guo ZhengDivision of Rheumatology, Department of Medicine, Penn State Hershey College of Medicine, Hershey, PA, USA.
Junqi NiuDepartment of Hepatology, First Hospital, Jilin University, Changchun, Jilin, China.
Paul GalardyDepartment of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Xuemei TongShanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guochao ShiDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huabin LiENT Department, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-2477-2879
Fan PanImmunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-4187-5095
Bin LiShanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0002-7640-8884
Shanghai Jiao Tong University · CNJohns Hopkins University · USFirst Affiliated Hospital of Zhengzhou University · CNChina International Science and Technology Cooperation · CNEye & ENT Hospital of Fudan University · CNMayo Clinic in Florida · USPenn State Milton S. Hershey Medical Center · USInstitut Pasteur of Shanghai · CNJilin University · CNRoswell Park Comprehensive Cancer Center · US
Funding
Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6ME3 ligase mediated control of Foxp3 expression and immune suppression-mechanisms and potential as immunotherapeutic targetR01AI137046 · NIAID · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M. · 2018 to 2022
$2.0MNCI NIH HHS P30 CA016056NIAID NIH HHS R01 AI137046
Abstract
The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-β induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.
Indexed as
Forkhead Transcription FactorsT-Lymphocytes, RegulatoryHumansInflammationTransforming Growth Factor betaUbiquitin-Specific Peptidase 7Ubiquitin ThiolesteraseForkhead Transcription FactorsFOXP3 protein, humanTransforming Growth Factor betaUbiquitin-Specific Peptidase 7Ubiquitin ThiolesteraseUSP44 protein, humanUSP7 protein, humandeubiquitinaseFOXP3induced regulatory T cellstumor immunityUSP44
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