Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication

被引：112

作者：

Liao, Tsai-Ling ^{[1
,2
,3
]}

Wu, Chung-Yi ^{[1
]}

Su, Wen-Chi ^{[1
]}

Jeng, King-Song ^{[1
]}

Lai, Michael M. C. ^{[1
,2
,4
,5
]}

机构：

[1] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan

[2] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 10764, Taiwan

[3] Ctr Dis Control, Dept Hlth, Res & Diagnost Ctr, Taipei, Taiwan

[4] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA USA

[5] Natl Cheng Kung Univ, Tainan 70101, Taiwan

来源：

EMBO JOURNAL | 2010年 / 29卷 / 22期

关键词：

influenza A virus; NP; USP11; POLYMERASE-II; DNA-DAMAGE; NUCLEOPROTEIN; INTERACTS; SCREEN; USP11; INFECTION; SYSTEM; ENZYME; IDENTIFICATION;

D O I：

10.1038/emboj.2010.250

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：

Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/ deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited viral genomic RNA replication, and this inhibition required the deubiquitinase activity. Furthermore, we showed that USP11 interacted with PB2, PA, and NP of viral RNA replication complex, and that NP is a monoubi-quitinated protein and can be deubiquitinated by USP11 in vivo. Finally, we identified K184 as the ubiquitination site on NP and this residue is crucial for virus RNA replication. We propose that ubiquitination/deubiquitination of NP can be manipulated for antiviral therapeutic purposes.

引用

页码：3879 / 3890

页数：12

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[31] NPI-1,THE HUMAN HOMOLOG OF SRP-1, INTERACTS WITH INFLUENZA-VIRUS NUCLEOPROTEIN [J].