title: Poly(ADP-ribosyl)ation of FOXP3 Protein Mediated by PARP-1 Protein Regulates the Function of Regulatory T Cells.
abstract: Poly(ADP-ribose) polymerase 1 (PARP-1) is an ADP-ribosylating enzyme participating in diverse cellular functions. The roles of PARP-1 in the immune system, however, have not been well understood. Here we find that PARP-1 interacts with FOXP3 and induces its poly(ADP-ribosyl)ation. By using PARP-1 inhibitors, we show that reduced poly(ADP-ribosyl)ation of FOXP3 results in not only FOXP3 stabilization and increased FOXP3 downstream genes but also enhanced suppressive function of regulatory T cells. Our results suggest that PARP-1 negatively regulates the suppressive function of Treg cells at the posttranslational level via FOXP3 poly(ADP-ribosyl)ation. This finding has implications for developing PARP-1 inhibitors as potential agents for the prevention and treatment of autoimmune diseases.
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xuerui
authors.initials: X
authors.lastname: Luo
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Nie
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuaiwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zuojia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: the Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland, 20892-2190.
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: the Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-2170.
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.affiliation: From the Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, binli@sibs.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D055550:Protein Stability; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011064:Poly Adenosine Diphosphate Ribose; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: ADP-ribosylation; T cell; forkhead box P3 (FOXP3); immunosuppression; inhibitor; posttranscriptional regulation; regulatory T cell