tetano
Editor, Senior Moderator
J Biol Chem
. 2022 Jan 20;101611.
doi: 10.1016/j.jbc.2022.101611. Online ahead of print.
TRIM34 modulates influenza virus-activated programmed cell death by targeting Z-DNA-binding protein 1 for K63-linked polyubiquitination
Xiaoyan Wang[SUP] 1 [/SUP], Jing Xiong[SUP] 1 [/SUP], Diwei Zhou[SUP] 2 [/SUP], Shanfeng Zhang[SUP] 3 [/SUP], Li Wang[SUP] 4 [/SUP], Qingqing Tian[SUP] 5 [/SUP], Changming Li[SUP] 1 [/SUP], Jie Liu[SUP] 1 [/SUP], Yaping Wu[SUP] 6 [/SUP], Junying Li[SUP] 7 [/SUP], Jun Wang[SUP] 8 [/SUP]
Affiliations
Abstract
Z-DNA-binding protein 1 (ZBP1) is an innate sensor of influenza A virus (IAV) that participates in IAV-induced programmed cell death. Nevertheless, little is known about the upstream signaling pathways regulating ZBP1. We found that a member of the tripartite motif (TRIM) family, TRIM34, interacted with ZBP1 to promote its K63-linked polyubiquitination. Using a series of genetic approaches, we provide in vitro and in vivo evidence indicating that IAV triggered cell death and inflammatory responses via dependent on TRIM34/ZBP1 interaction. TRIM34 and ZBP1 expression and interaction protected mice from death during IAV infection owing to reduced inflammatory responses and epithelial damage. Additionally, analysis of clinical samples revealed that TRIM34 associates with ZBP1 and mediates ZBP1 polyubiquitination in vivo. Higher levels of proinflammatory cytokines correlated with higher levels of ZBP1 in IAV-infected patients. Taken together, we conclude that TRIM34 serves as a critical regulator of IAV-induced programmed cell death by mediating the K63-linked polyubiquitination of ZBP1.
Keywords: Influenza A virus; Programmed cell death; TRIM34; ZBP1; polyubiquitination.
. 2022 Jan 20;101611.
doi: 10.1016/j.jbc.2022.101611. Online ahead of print.
TRIM34 modulates influenza virus-activated programmed cell death by targeting Z-DNA-binding protein 1 for K63-linked polyubiquitination
Xiaoyan Wang[SUP] 1 [/SUP], Jing Xiong[SUP] 1 [/SUP], Diwei Zhou[SUP] 2 [/SUP], Shanfeng Zhang[SUP] 3 [/SUP], Li Wang[SUP] 4 [/SUP], Qingqing Tian[SUP] 5 [/SUP], Changming Li[SUP] 1 [/SUP], Jie Liu[SUP] 1 [/SUP], Yaping Wu[SUP] 6 [/SUP], Junying Li[SUP] 7 [/SUP], Jun Wang[SUP] 8 [/SUP]
Affiliations
- PMID: 35065966
- DOI: 10.1016/j.jbc.2022.101611
Abstract
Z-DNA-binding protein 1 (ZBP1) is an innate sensor of influenza A virus (IAV) that participates in IAV-induced programmed cell death. Nevertheless, little is known about the upstream signaling pathways regulating ZBP1. We found that a member of the tripartite motif (TRIM) family, TRIM34, interacted with ZBP1 to promote its K63-linked polyubiquitination. Using a series of genetic approaches, we provide in vitro and in vivo evidence indicating that IAV triggered cell death and inflammatory responses via dependent on TRIM34/ZBP1 interaction. TRIM34 and ZBP1 expression and interaction protected mice from death during IAV infection owing to reduced inflammatory responses and epithelial damage. Additionally, analysis of clinical samples revealed that TRIM34 associates with ZBP1 and mediates ZBP1 polyubiquitination in vivo. Higher levels of proinflammatory cytokines correlated with higher levels of ZBP1 in IAV-infected patients. Taken together, we conclude that TRIM34 serves as a critical regulator of IAV-induced programmed cell death by mediating the K63-linked polyubiquitination of ZBP1.
Keywords: Influenza A virus; Programmed cell death; TRIM34; ZBP1; polyubiquitination.