DDX41 binds viral dsDNA

Stable Identifier
R-HSA-3134822
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human herpesvirus 1, Vaccinia virus
Compartment
cytosol
ReviewStatus
5/5
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DDX41 binds viral dsDNA
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The helicase DDX41 was shown to sense exogenous DNA in human and mouse cells (Zhang Z et al. 2011, Parvatiyar K et al. 2012). DDX41 was also reported to sense and interact with bacterial secondary messengers cyclic di-GMP or cyclic di-AMP (Parvatiyar K et al. 2012). Mutagenesis analysis with DDX41 deletion constructs revealed that the central DEAD-box domain of DDX41 mediated the binding with DNA (Zhang Z et al. 2011, Parvatiyar K et al. 2012). Knockdown of DDX41 or STING in human cells (THP-1 and PBMC cells) and mouse dendritic cells significantly reduced the cytokine production in response to pathogen-derived DNA or poly(dG:dC) (Zhang Z et al. 2011, Parvatiyar K et al. 2012). DDX41 localized together with STING in the cytoplasm when both DDX41 and STING were co-expressed in HEK293T cells (Zhang Z et al. 2011). Mouse Ddx41 was found to bind Sting and Tbk1 in both resting and poly(dA:dT)-stimulated mouse splenic myeloid dendritic cell (D2SC mDCs) (Zhang Z et al. 2011). Ddx41-Sting interaction was also observed in c-di-GMP- or c-di-AMP-treated D2SC cells (Parvatiyar K et al. 2012). Moreover, knockdown of Ddx41 or Sting inhibited phosphorylation of Tbk1, Irf3, p65 subunit of NF-kappaB and other signal transducers in DNA-stimulated mouse bone marrow-derived (BMDCs) and D2SC cells (Zhang Z et al. 2011, Parvatiyar K et al. 2012). Collectively, these data suggest that DNA triggers DDX41 downstream signaling to type I interferon in a STING-dependent manner.

The E3 ubiquitin ligase TRIM21 was reported to promote the K48-linked ubiquitination and degradation of DDX41 leading to downregulation of the type I interferon production in mouse mDC and human monocytes THP-1 (Zhang Z et al. 2013).

Literature References
PubMed ID Title Journal Year
21892174 The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells

Yuan, B, Lu, N, Kim, T, Zhang, Z, Liu, YJ, Bao, M

Nat. Immunol. 2011
23222971 The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA

Yuan, B, Weng, L, Lu, N, Zhang, Z, Liu, YJ, Bao, M

Nat. Immunol. 2012
23142775 The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response

Zeng, S, Schenk, M, Parvatiyar, K, Cheng, G, Liu, YJ, Zaver, SA, Iyer, SS, Liu, ZJ, Ouyang, S, Zhang, Z, Modlin, RL, Teles, RM, Zhong, W, Jiang, Y

Nat. Immunol. 2012
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
TRIM21 [cytosol] (Homo sapiens)
Authored
Shamovsky, V  (2013-02-06)
Reviewed
Wu, J  (2013-05-22)
Jin, L  (2013-05-22)
D'Eustachio, P  (2013-02-11)
Created
Shamovsky, V  (2013-02-13)
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