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Significant functional difference between $\small \textit{TNFAIP3}$ truncation and missense mutants

Published version
Peer-reviewed

Type

Article

Change log

Authors

Escudero-Ibarz, L 
Wang, M 
Du, M-Q 

Abstract

A20, encoded by TNFAIP3, is a molecular “brake” of the canonical NF-κB activation pathway and attenuates the NF-κB activity triggered by a number of surface receptors.1,2 A20 contains an N-terminal OTU domain that possesses deubiquitinating activity, and 7 zinc finger (ZF) domains in its C-terminus that confers the E3 ubiquitin ligase activity.3 Through removing the K63-linked ubiquitin chain, catalysing the K48-linked polyubiquitination, and also direct binding to the linear polyubiquitin chain of its targets, A20 can inactivate a number of NF-κB positive regulators, including RIP1/2, TRAF6, Ubc13 and NEMO, thus negatively regulating the signalling of several surface receptors, including BCR, TNFR, TLR and IL1βR.1,2,4 A20 itself is a transcriptional target of NF-κB, and its transcriptional activation by NF-κB thus serves as an auto-negative feedback to attenuate NF-κB activities triggered by these receptor signallings.1,2

Description

Keywords

NF-κB activation, TNFAIP3 mutation

Journal Title

Haematologica

Conference Name

Journal ISSN

0390-6078
1592-8721

Volume Title

101

Publisher

Ferrata Storti Foundation
Sponsorship
Bloodwise, UK, Addenbrooke’s Charitable Trust, Pathological Society of UK and Ireland