A20, also referred to as TNF-α-induced protein 3 (TNFAIP3), is cytokine-inducible protein that functions to inhibit apoptosis and activate NFκB.Specifically, A20 is induced by tumor necrosis factor (TNF) and interleukin 1 (IL-1), and acts as a negative regulator of nuclear factor κ B (NFκB) gene expression. By inhibiting NFκB activation, A20 plays a critical role in terminating NFκB responses to various stimuli. Studies also show that A20 contains site-specific ubiquitin modifying activity that can contribute to its biological functions. The amino-terminus of A20 contains de-ubiquitinating (DUB) activity for Lys63 branches, such as those found in TRAF6 and RIP, while the carboxyl-terminus contains ubiquitin ligase (E3) activity for Lys48 branches of the same substrates and leads to their degradation.
