title: NF-κB downregulates Cbl-b through binding and suppressing Cbl-b promoter in T cell activation.
abstract: T cell activation causes the translocation of NF-κB dimers from the cytoplasm into the nucleus where NF-κB regulates inflammatory and immune response genes. Cbl-b is a negative regulator of T cell activation. However, the correlation between NF-κB activity and Cbl-b expression remains unclear. We showed that IκBαΔN-Tg T cells exhibited less NF-κB activity but higher levels of Cbl-b when compared with wild-type T cells. Furthermore, ursolic acid suppressed NF-κB activation and inhibited the downregulation of Cbl-b in wild-type T cells. NF-κBp65 specifically bound to an 11-bp NF-κB consensus sequence (gcaggaagtcc) in the Cbl-b promoter. Binding of NF-κB to this sequence suppressed Cbl-b transcription, thereby resulting in the negative regulation of Cbl-b expression. In addition, Cbl-b knockout led to the loss of cardiac allograft tolerance in IκBαΔN-Tg mice. These results indicated that NF-κB downregulated Cbl-b by binding and suppressing Cbl-b promoter in T cell activation. Our findings provide a novel role for NF-κB signaling in T cell activation.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: St.-Antonius-Hospital Kleve, Katholisches Karl-Leisner-Klinikum, Kleve 47533, Germany;
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Ministry of Health, and Key Laboratory of Ministry of Education, 430030 Wuhan, China;
authors.forename: LiMin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Center Hospital of TaiAn, 271000 TaiAn, China;
authors.forename: MingQiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of General Surgery, Tianjin Union Medical Center, 300000 Tianjin, China; and.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Transplant Center, Zhongnan Hospital of Wuhan University, 430060 Wuhan, China.
authors.forename: ChengBiao
authors.initials: C
authors.lastname: Xue
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Ministry of Health, and Key Laboratory of Ministry of Education, 430030 Wuhan, China;
authors.forename: Xia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Ministry of Health, and Key Laboratory of Ministry of Education, 430030 Wuhan, China; pzhou@tjh.tjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D064591:Allografts; D000818:Animals; D055785:Gene Knockdown Techniques; D016027:Heart Transplantation; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000276:immunology*; D020218:Response Elements / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology*; D023001:Transplantation Tolerance
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D050721:Proto-Oncogene Proteins c-cbl