The 11S Proteasome Subunit PSME3 Is a Positive Feedforward Regulator of NF-κB and Important for Host Defense against Bacterial Pathogens

被引：47

作者：

Sun, Jinxia ^{[1
,2
]}

Luan, Yi ^{[1
,2
]}

Xiang, Dong ^{[1
,2
]}

Tan, Xiao ^{[1
,2
]}

Chen, Hui ^{[1
,2
]}

Deng, Qi ^{[1
,2
]}

Zhang, Jiaojiao ^{[1
,2
]}

Chen, Minghui ^{[1
,2
]}

Huang, Hongjun ^{[1
,2
]}

Wang, Weichao ^{[1
,2
]}

Niu, Tingting ^{[1
,2
]}

Li, Wenjie ^{[5
]}

Peng, Hu ^{[5
]}

Li, Shuangxi ^{[1
,2
]}

Li, Lei ^{[1
,2
]}

Tang, Wenwen ^{[3
]}

Li, Xiaotao ^{[1
,2
]}

Wu, Dianqing ^{[4
]}

Wang, Ping ^{[1
,2
,3
]}

机构：

[1] E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[2] E China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[3] Tongji Univ, Sch Life Sci & Technol, Shanghai Peoples Hosp 10, Dept Cent Lab, Shanghai 200072, Peoples R China

[4] Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA

[5] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Emergency Dept, Shanghai 200072, Peoples R China

来源：

CELL REPORTS | 2016年 / 14卷 / 04期

基金：

中国国家自然科学基金; 国家教育部博士点专项基金资助;

关键词：

REG-GAMMA-PROTEASOME; KRUPPEL-LIKE FACTOR; INFLAMMATORY RESPONSE; IMMUNE-RESPONSE; INNATE IMMUNITY; KLF2; DEGRADATION; PATHWAY; UBIQUITINATION; ACTIVATION;

D O I：

10.1016/j.celrep.2015.12.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The NF-kappa B pathway plays important roles in immune responses. Although its regulation has been extensively studied, here, we report an unknown feedforward mechanism for the regulation of this pathway by Toll-like receptor (TLR) ligands in macrophages. During bacterial infections, TLR ligands upregulate the expression of the 11S proteasome subunit PSME3 via NF-kappa B-mediated transcription in macrophages. PSME3, in turn, enhances the transcriptional activity of NF-kappa B by directly binding to and destabilizing KLF2, a negative regulator of NF-kappa B transcriptional activity. Consistent with this positive role of PSME3 in NF-kappa B regulation and importance of the NF-kappa B pathway in host defense against bacterial infections, the lack of PSME3 in hematopoietic cells renders the hosts more susceptible to bacterial infections, accompanied by increased bacterial burdens in host tissues. Thus, this study identifies a substrate for PSME3 and elucidates a proteolysis-dependent, but ubiquitin-independent, mechanism for NF-kappa B regulation that is important for host defense and innate immunity.

引用

页码：737 / 749

页数：13