摘要
The NF-κB transcription factor is a central mediator of inflammatory and innate immune signaling pathways. Activation of NF-KB is achieved by K63-1inked polyubiquitination of key signaling molecules which recruit kinase complexes that in turn activate the IKB kinase （IKK）. Ubiquitination is a highly dynamic process and is balanced by deubiquitinases that cleave polyubiquitin chains and terminate downstream signaling events. The A20 deubiquitinase is a critical negative regulator of NF-κB and inflammation, since A20-deficient mice develop uncontrolled and spontaneous multi-organ inflammation. Furthermore, specific polymorphisms in the A20 genomic locus predispose humans to autoimmune disease. Recent studies also indicate that A20 is an important tumor suppressor that is inactivated in B-cell lymphomas. Therefore, targeting A20 may form the basis of novel therapies for autoimmune disease and lymphomas.
The NF-κB transcription factor is a central mediator of inflammatory and innate immune signaling pathways. Activation of NF-KB is achieved by K63-1inked polyubiquitination of key signaling molecules which recruit kinase complexes that in turn activate the IKB kinase （IKK）. Ubiquitination is a highly dynamic process and is balanced by deubiquitinases that cleave polyubiquitin chains and terminate downstream signaling events. The A20 deubiquitinase is a critical negative regulator of NF-κB and inflammation, since A20-deficient mice develop uncontrolled and spontaneous multi-organ inflammation. Furthermore, specific polymorphisms in the A20 genomic locus predispose humans to autoimmune disease. Recent studies also indicate that A20 is an important tumor suppressor that is inactivated in B-cell lymphomas. Therefore, targeting A20 may form the basis of novel therapies for autoimmune disease and lymphomas.
