N-MYC -interacting protein enhances type II interferon signaling by inhibiting STAT1 sumoylation

被引：3

作者：

Feng, Linyuan ^{[1
,2
]}

Li, Wanwei ^{[1
]}

Li, Xiaowen ^{[1
]}

Li, Xiaotian ^{[1
]}

Ran, Yanhong ^{[1
]}

Yang, Xiaoping ^{[1
]}

Deng, Zemin ^{[1
]}

Li, Hongjian ^{[1
,3
,4
]}

机构：

[1] Jinan Univ, Coll Life Sci & Technol, Dept Biotechnol, Guangzhou, Peoples R China

[2] Southern Med Univ, Guangdong Prov Peoples Hosp, Med Res Inst, Guangdong Acad Med Sci, Guangzhou, Peoples R China

[3] Jinan Univ, Stat Key Lab Bioact Mol & Druggabil Assessment, Guangzhou, Peoples R China

[4] Jinan Univ, Coll Life Sci & Technol, Dept Biotechnol, Guangzhou 510632, Guangdong, Peoples R China

来源：

FASEB JOURNAL | 2023年 / 37卷 / 12期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

interferon-gamma; NMI protein; phosphorylation; STAT1 transcription factor; sumoylation; OF-FUNCTION MUTATIONS; OXIDE SYNTHASE GENE; NITRIC-OXIDE; TARGETED DISRUPTION; SUMO-1; CONJUGATION; INNATE IMMUNITY; IFN-GAMMA; UBC9; TRANSCRIPTION; ACTIVATION;

D O I：

10.1096/fj.202301450RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Signaling desensitization is key to limiting signal transduction duration and intensity. Signal transducer and activator of transcription 1 (STAT1) can mediate type II interferon (IFN gamma)-induced immune responses, which are enhanced and inhibited by STAT1 phosphorylation and sumoylation, respectively. Here, we identified an N-MYC interacting protein, NMI, which can enhance STAT1 phosphorylation and STAT1-mediated IFN gamma immune responses by binding and sequestering the E2 SUMO conjugation enzyme, UBC9, and blocking STAT1 sumoylation. NMI facilitates UBC9 nucleus-to-cytoplasm translocation in response to IFN gamma, thereby inhibiting STAT1 sumoylation. STAT1 phosphorylation at Y701 and sumoylation at K703 are mutually exclusive modifications that regulate IFN gamma-dependent transcriptional responses. NMI could not alter the phosphorylation level of sumoylation-deficient STAT1 after IFN gamma treatment. Thus, IFN gamma signaling is modulated by NMI through sequestration of UBC9 in the cytoplasm, leading to inhibition of STAT1 sumoylation. Hence, NMI functions as a switch for STAT1 activation/inactivation cycles by modulating an IFN gamma-induced desensitization mechanism.

引用

页数：15