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Updated: May 23, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Regulation of NF-κB by deubiquitinases
Edward W Harhaj1, Vishva M Dixit
1Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL, USA.
Abstract:
The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF-κB signaling and the resolution of inflammation. In this review, we focus on NF-κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer.
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