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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 32, Number 11
BKCSDE 32(11)
November 20, 2011 

The Role of Transglutaminase in Double-stranded DNA-Triggered Antiviral Innate Immune Response
Jae-Wook Yoo, Sun Woo Hong, Shambhunath Bose, Hojun Kim, Soo Youl Kim, Soyoun Kim, Dong-ki Lee*,
dsDNA, Innate immunity, TIG3, Transglutaminase
Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-κB transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-κB activity by inducing IκBα polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.
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