Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification

He Xin Shi, Kai Yang, Xing Liu, Xin Yi Liu, Bo Wei, Yu Fei Shan, Lian Hui Zhu, Chen Wang

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Virus infection induces host antiviral responses, including induction of type I interferons. Transcription factor interferon regulatory factor 3 (IRF3) plays a pivotal role and is tightly regulated in this process. Here, we identify HERC5 (HECT domain and RLD 5) as a specific binding protein of IRF3 by immunoprecipitation. Ectopic expression or knockdown of HERC5 could, respectively, enhance or impair IRF3-mediated gene expression. Mechanistically, HERC5 catalyzes the conjugation of ubiquitin-like protein ISG15 onto IRF3 (Lys193, -360, and -366), thus attenuating the interaction between Pin1 and IRF3, resulting in sustained IRF3 activation. In contrast to results for wild-type IRF3, the mutant IRF3(K193,360,366R) interacts tightly with Pin1, is highly polyubiquitinated, and becomes less stable upon Sendai virus (SeV) infection. Consistently, host antiviral responses are obviously boosted or crippled in the presence or absence of HERC5, respectively. Collectively, this study characterizes HERC5 as a positive regulator of innate antiviral responses. It sustains IRF3 activation via a novel posttranslational modification, ISGylation.

Original languageEnglish (US)
Pages (from-to)2424-2436
Number of pages13
JournalMolecular and Cellular Biology
Volume30
Issue number10
DOIs
StatePublished - May 1 2010

Fingerprint

Interferon Regulatory Factor-3
Antiviral Agents
Virus Diseases
Ubiquitins
Sendai virus
Interferon Type I
Post Translational Protein Processing
Immunoprecipitation
Carrier Proteins
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. / Shi, He Xin; Yang, Kai; Liu, Xing; Liu, Xin Yi; Wei, Bo; Shan, Yu Fei; Zhu, Lian Hui; Wang, Chen.

In: Molecular and Cellular Biology, Vol. 30, No. 10, 01.05.2010, p. 2424-2436.

Research output: Contribution to journalArticle

Shi, He Xin ; Yang, Kai ; Liu, Xing ; Liu, Xin Yi ; Wei, Bo ; Shan, Yu Fei ; Zhu, Lian Hui ; Wang, Chen. / Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 10. pp. 2424-2436.
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