IFI16 binds cytosolic dsDNA

Stable Identifier
R-HSA-1834951
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1, Human herpesvirus 1, Listeria monocytogenes, Vaccinia virus
Compartment
cytosol
ReviewStatus
5/5
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IFI16 binds cytosolic dsDNA
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Interferon (IFN)-inducible IFI16 protein was shown to be critical for type I IFN and pro inflammatory responses in viral DNA-stimulated human and mouse cells [Unterholzner L et al 2010; Kerur N et al 2011; Li T et al 2012]. Despite being predominantly nuclear, IFI16 can sense pathogenic DNA in both the cytoplasm and the nucleus. Cytosolic IFI16 can directly bind viral dsDNA motifs via its HIN200 domains in human monocytic leukemia THP-1 cell extracts. IFI16-mediated response to cytosolic DNA was reported to induce type I IFN production in a STING-TBK1- and IRF3 dependent manner [Unterholzner L et al 2010].

Nuclear IFI16 can detect kaposi sarcoma-associated herpesvirus (KSHV) DNA which results in IL-1beta maturation and caspase-1 inflammasome activation in human cells [Kerur N et al 2011]. Importantly, acetylation of the nuclear localization signal (NLS) of IFI16 in lymphocytes and macrophages leads to cytosolic accumulation of IFI16 and is important for its type I IFN stimulation ability in cytoplasm [Li T et al 2012].

Literature References
PubMed ID Title Journal Year
22691496 Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16

Li, T, Diner, BA, Chen, J, Cristea, IM

Proc. Natl. Acad. Sci. U.S.A. 2012
21575908 IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection

Kerur, N, Veettil, MV, Sharma-Walia, N, Bottero, V, Sadagopan, S, Otageri, P, Chandran, B

Cell Host Microbe 2011
20890285 IFI16 is an innate immune sensor for intracellular DNA

Unterholzner, L, Keating, SE, Baran, M, Horan, KA, Jensen, SB, Sharma, S, Sirois, CM, Jin, T, Latz, E, Xiao, TS, Fitzgerald, KA, Paludan, SR, Bowie, AG

Nat Immunol 2010
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Authored
Shamovsky, V  (2012-07-09)
Reviewed
D'Eustachio, P  (2012-07-18)
Jin, L  (2012-08-18)
Wu, J  (2013-05-22)
Created
Shamovsky, V  (2011-10-27)
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