Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA

被引：61

作者：

Liu, Shuo ^{[1
,2
]}

Jiang, Minghong ^{[1
,2
]}

Wang, Wendie ^{[1
,2
]}

Liu, Wei ^{[1
,2
]}

Song, Xiaoqi ^{[1
,2
]}

Ma, Zhongfei ^{[1
,2
]}

Zhang, Shikun ^{[1
,2
]}

Liu, Lun ^{[1
,2
]}

Liu, Yin ^{[1
,2
]}

Cao, Xuetao ^{[1
,2
,3
,4
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Dept Immunol, Beijing, Peoples R China

[2] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Ctr Immunotherapy, Beijing, Peoples R China

[3] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai, Peoples R China

[4] Second Mil Med Univ, Inst Immunol, Shanghai, Peoples R China

来源：

NATURE IMMUNOLOGY | 2018年 / 19卷 / 01期

基金：

中国国家自然科学基金;

关键词：

CHRONIC MUCOCUTANEOUS CANDIDIASIS; TRANSCRIPTION FACTOR STAT1; PERSISTENT LCMV INFECTION; UBIQUITIN E3 LIGASE; GENE-EXPRESSION; RING1B; DEGRADATION; CHROMATIN; BINDING; POLYUBIQUITINATION;

D O I：

10.1038/s41590-017-0003-0

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound toSTAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.

引用

页码：41 / +

页数：13

共 40 条

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