Your browser doesn't support javascript.
loading
The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
Yang, Jing; Wei, Ping; Barbi, Joseph; Huang, Qianru; Yang, Evan; Bai, Yakun; Nie, Jia; Gao, Yanhang; Tao, Jinhui; Lu, Ying; Xie, Chichu; Hou, Xiaoxia; Ren, Jiazi; Wu, Xingmei; Meng, Jian; Zhang, Ying; Fu, Juan; Kou, Wei; Gao, Yayi; Chen, Zuojia; Liang, Rui; Tsun, Andy; Li, Dan; Guo, Wenzhi; Zhang, Shuijun; Zheng, Song-Guo; Niu, Junqi; Galardy, Paul; Tong, Xuemei; Shi, Guochao; Li, Huabin; Pan, Fan; Li, Bin.
Afiliación
  • Yang J; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wei P; 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 Hos
  • Barbi J; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Huang Q; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yang E; Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bai Y; Henan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
  • Nie J; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Gao Y; Key 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.
  • Tao J; Department of Hepatology, First Hospital, Jilin University, Changchun, Jilin, China.
  • Lu Y; Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Xie C; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Hou X; Division of Rheumatology, Department of Medicine, Penn State Hershey College of Medicine, Hershey, PA, USA.
  • Ren J; Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wu X; Key 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.
  • Meng J; ENT Department, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.
  • Zhang Y; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Fu J; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
  • Kou W; Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gao Y; 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 Hos
  • Chen Z; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Liang R; Key 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.
  • Tsun A; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Li D; Key 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.
  • Guo W; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Zhang S; Key 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.
  • Zheng SG; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Niu J; Key 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.
  • Galardy P; Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Tong X; Key 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.
  • Shi G; Henan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
  • Li H; Henan Key Laboratory of Digestive Organ Transplantation, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.
  • Pan F; Division of Rheumatology, Department of Medicine, Penn State Hershey College of Medicine, Hershey, PA, USA.
  • Li B; Department of Hepatology, First Hospital, Jilin University, Changchun, Jilin, China.
EMBO Rep ; 21(9): e50308, 2020 09 03.
Article en En | MEDLINE | ID: mdl-32644293
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-ß 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.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Factores de Transcripción Forkhead Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Factores de Transcripción Forkhead Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: China