SARS-CoV-2 N binds TAK1

Stable Identifier
R-HSA-9755757
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
ReviewStatus
5/5
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General
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Several studies showed that viral RNA binding to SARS-CoV-2 nucleocapsid (N) protein induces liquid-liquid phase separation (LLPS) (Wu Y et al. 2021; Wang S et al. 2021; Cubuk J et al. 2021; Lu S et al. 2021). Viral N protein:RNA LLPS recruits TGF-beta-activated kinase 1 (TAK1) and IκB kinase (IKK) complexes and enhances their interaction which in turn promotes NF-kappaB activation and expression of pro-inflammatory cytokines (Wu Y et al. 2021). The C-terminal domain (CTD) of viral N is essential for LLPS (Wu Y et al. 2021; Wang S et al. 2021) and induction of NF-kappaB signaling in mammalian cells (Wu Y et al. 2021). Deletion of CTD abolished SARS-CoV-2 N LLPS and the recruitment of TAK1/IKK complexes. Co-immunoprecipitation analysis revealed that SARS-CoV-2 N protein interacted with the components of the TAK1 complex and the IKK complex, including TAK1, TAB1, TAB2, IKBKA (CHUK), IKBKB, and NEMO (IKBKG) upon co-expression in human embryonic kidney 293T (HEK293T) cells (Wu Y et al. 2021). Endogenous IKK and TAK1 immunoprecipitated together with N in human lung cancer Calu3 cells infected with SARS-CoV-2. Immunofluorescence analysis further revealed the enhanced co-localization between N protein and IKBKB after SARS-CoV-2 infection in human hepatoma Huh7 cells. These data sugget that SARS-CoV-2 N:RNA LLPS serves as a platform to enhance the interaction between TAK1 and IKK complexes promoting NF-kappaB-dependent inflammatory responses (Wu Y et al. 2021).

Literature References
PubMed ID Title Journal Year
33895773 RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation

Xie, W, Ma, L, Zhao, J, Zhao, Z, Cai, S, Zhou, L, Cui, J, Jin, S, Zhang, L, Wu, Y, Zhuang, Z

Signal Transduct Target Ther 2021
Participants
Participates
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Reviewed
Created
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