E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1.

Abstract:

:TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo. Our study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Song G,Liu B,Li Z,Wu H,Wang P,Zhao K,Jiang G,Zhang L,Gao C

doi

10.1038/ni.3588

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

1342-1351

issue

12

eissn

1529-2908

issn

1529-2916

pii

ni.3588

journal_volume

17

pub_type

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