http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
OTUD7B controls non-canonical NF-kB activation through deubiquitination of TRAF3
( Hongbo Hu ),( George C Brittain ),( Jae Hoon Chang ),( Nahum Puebla Osorio ),( Jin Jin ),( Anna Zal ),( Yichuan Xiao ),( Xuhong Cheng ),( Mikyoung Chang ),( Yang Xin Fu ),( Tomasz Zal ),( Chengming 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
The non-canonical NF-κB pathway forms a major arm of NF-κB signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival. Activation of the non-canonical NF-κB pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown. Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-κB pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-κB activation but causes hyperactivation of non-canonical NF-κB. In response to non-canonical NF-κB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-κB activation. Consequently, the OTUD7Bdeficiency results in B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa, and elevated host-defence ability against an intestinal bacterial pathogen, Citrobacter rodentium. These findings establish OTUD7B as a crucial regulator of signal-inducednon-canonical NF-κB activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.
The Kinase TBK1 controls lgA class switching by negatively regulating noncanonical NF-kF dignaling
( Jin Jin ),( Yichuan Xiao ),( Jae Hoon Chang ),( Jiayi Yu ),( Hongbo Hu ),( Robyn Starr ),( George C Brittain ),( Mikyoung Chang ),( Xuhong Cheng ),( Shao Cong Sun ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify thekinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell-specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switchingby attenuating noncanonical signaling via the transcription factor NF-κB, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and identify a unique mechanism that controls IgA production.
Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation
( Yichuan Xiao ),( Jin Jin ),( Mikyoung Chang ),( Jae Hoon Chang ),( Hongbo Hu ),( Xiaofei Zhou ),( George C Brittain ),( Christine Stansberg ),( Qivind Torkildsen ),( Xiaodong Wang ),( Robert Brink ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
Microglia are crucial for the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Here we show that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and promotes microglial activation during the course of EAE induction. Peli1mediates the induction of chemokines and proinflammatory cytokines in microglia and therebypromotes recruitment of T cells into the central nervous system. The severity of EAE is reduced inPeli1-deficient mice despite their competent induction of inflammatory T cells in the peripheral lymphoid organs. Notably, Peli1 regulates Toll-like receptor (TLR) pathway signaling by promoting degradation of TNF receptor-associated factor 3 (Traf3), a potent inhibitor of mitogen-activated protein kinase (MAPK) activation and gene induction. Ablation of Traf3 restores microglial activation and CNS inflammation after the induction of EAE in Peli1-deficient mice. These findings establish Peli1 as a microglia-specific mediator of autoimmune neuroinflammation and suggest a previously unknown signaling mechanism of Peli1 function.