TY - JOUR
T1 - The DEAH-Box RNA helicase DHX15 activates NF-κB and MAPK signaling downstream of MAVS during antiviral responses
AU - Mosallanejad, Kenta
AU - Sekine, Yusuke
AU - Ishikura-Kinoshita, Seiko
AU - Kumagai, Kazuo
AU - Nagano, Tetsuo
AU - Matsuzawa, Atsushi
AU - Takeda, Kohsuke
AU - Naguro, Isao
AU - Ichijo, Hidenori
PY - 2014/4/29
Y1 - 2014/4/29
N2 - During infection with an RNA virus, the DExD/H-box RNA helicases RIG-I (retinoic acid-inducible gene I) and MDA5 (melanoma differentiation-associated gene 5) activate the interferon regulatory factor 3 (IRF3), nuclear factor κB (NF-κB), c-Jun amino-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways through an unknown mechanism involving the adaptor protein MAVS (mitochondrial antiviral signaling). We used a Drosophila misexpression screen to identify DEAH-box polypeptide 15 (DHX15) as an activator of the p38 MAPK pathway. Human DHX15 contributed to the activation of the NF-κB, JNK, and p38 MAPK pathways, but not the IRF3 pathway, in response to the synthetic double-stranded RNA analog poly(I:C) (polyinosinic-polycytidylic acid), and DHX15 was required for optimal cytokine production in response to poly(I:C) and infection with RNA virus. DHX15 physically interacted with MAVS and mediated the MAVS-dependent activation of the NF-κB and MAPK pathways. Furthermore, DHX15 was required for poly(I:C)- and RNA virus-dependent, MAVS-mediated apoptosis. Thus, our findings indicate that, in RIG-I-like receptor signaling, DHX15 specifically stimulates the NF-κB and MAPK pathways downstream of MAVS and contributes to MAVS-mediated cytokine production and apoptosis.
AB - During infection with an RNA virus, the DExD/H-box RNA helicases RIG-I (retinoic acid-inducible gene I) and MDA5 (melanoma differentiation-associated gene 5) activate the interferon regulatory factor 3 (IRF3), nuclear factor κB (NF-κB), c-Jun amino-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways through an unknown mechanism involving the adaptor protein MAVS (mitochondrial antiviral signaling). We used a Drosophila misexpression screen to identify DEAH-box polypeptide 15 (DHX15) as an activator of the p38 MAPK pathway. Human DHX15 contributed to the activation of the NF-κB, JNK, and p38 MAPK pathways, but not the IRF3 pathway, in response to the synthetic double-stranded RNA analog poly(I:C) (polyinosinic-polycytidylic acid), and DHX15 was required for optimal cytokine production in response to poly(I:C) and infection with RNA virus. DHX15 physically interacted with MAVS and mediated the MAVS-dependent activation of the NF-κB and MAPK pathways. Furthermore, DHX15 was required for poly(I:C)- and RNA virus-dependent, MAVS-mediated apoptosis. Thus, our findings indicate that, in RIG-I-like receptor signaling, DHX15 specifically stimulates the NF-κB and MAPK pathways downstream of MAVS and contributes to MAVS-mediated cytokine production and apoptosis.
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U2 - 10.1126/scisignal.2004841
DO - 10.1126/scisignal.2004841
M3 - Article
C2 - 24782566
AN - SCOPUS:84899708360
VL - 7
JO - Science's STKE : signal transduction knowledge environment
JF - Science's STKE : signal transduction knowledge environment
SN - 1937-9145
IS - 323
M1 - ra40
ER -