DeubiquitinasesintheregulationofNF-κBsignaling细胞研究.pdfVIP

Cell Research (2010) :1-18. © 2010 IBCB, SIBS, CAS All rights reserved 1001-0602/10 $ 32.00 npg REVIEW /cr κ Deubiquitinases in the regulation of NF- B signaling 1 2 Edward W Harhaj , Vishva M Dixit 1Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA; 2Department of Physiological Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA Nuclear factor-kappa B (NF-κB) is a critical regulator of multiple biological functions including innate and adap- tive immunity and cell survival. Activation of NF-κB is tightly regulated to preclude chronic signaling that may lead to persistent inflammation and cancer. Ubiquitination of key signaling molecules by E3 ubiquitin ligases has emerged as an important regulatory mechanism for NF-κB signaling. Deubiquitinases (DUBs) counteract E3 ligases and there- fore play a prominent role in the downregulation of NF-κB signaling and homeostasis. Understanding the mecha- nisms of NF-κB downregulation by specific DUBs such as A20 and CYLD may provide therapeutic opportunities for the treatment of chronic inflammatory diseases and cancer. Keywords : deubiquitinases; NF-κB; IKK; A20; CYLD Cell Research advance online publication 30 November 2010; doi:10.1038/cr.2010.166 Introduction spectively, are precursor forms of the p50 and p52 NF- κB subunits [7]. Nuclear factor-kappa B (NF-κB)/Rel represents a e