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Cell Res. 2011 Jan;21(1):22-39. doi: 10.1038/cr.2010.166. Epub 2010 Nov 30.

Deubiquitinases in the regulation of NF-κB signaling.

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Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA.


Nuclear factor-kappa B (NF-κB) is a critical regulator of multiple biological functions including innate and adaptive 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 therefore play a prominent role in the downregulation of NF-κB signaling and homeostasis. Understanding the mechanisms 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.

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