IndraLab

Statements


| 11

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"USP22 interacted with IRF3 after viral infection in a KPNA2-dependent manner."

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"USP22 is associated with IRF3 after viral infection."

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"Knockdown of KPNA2 impaired virus-induced USP22-IRF3 association in MEFs ( xref ), indicating that USP22 interacts with IRF3 through KPNA2 after viral infection."

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"Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection."

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"In this context, we observed that IRF3(IL139/140AA), which is predominantly located in the nucleus, did not interact with USP22, and USP22(RR164/165AA) interacted with IRF3, as did wild-type USP22."

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"We observed that USP22 interacted with IRF3 and phosphorylated IRF3 (pIRF3) in the cytoplasm but not in the nucleus after vesicular stomatitis virus (VSV) or HSV-1 infection in BMDCs ( xref )."

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"Interestingly, we found that the USP22(RR164/165AA) was still associated with IRF3 ( xref )."

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"These data suggest that USP22 interacts with IRF3 in the cytoplasm after viral infection."

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"Because USP22-mediated virus-triggered signaling requires its enzyme activity and USP22 interacts with IRF3, we hypothesized that USP22 might catalyze deubiquitination of IRF3 and regulate the nuclear translocation of IRF3."

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"Together with the observations that knockdown of KPNA2 impaired IRF3-USP22 associations after viral infection and that reconstitution of KPNA2 into USP22 knockout cells restored virus-induced nuclear translocation of IRF3 and expression of downstream genes, we concluded that USP22 promotes nuclear translocation of IRF3 primarily through deubiquitinating and stabilizing KPNA2."

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"Such an intermediate protein should associate with both IRF3 and USP22 and promote virus-triggered signaling by facilitating the nuclear translocation of IRF3."