12 - Examination of Novel Signaling Programs in Innate Antiviral Immunity
University of California, Los Angeles
Microbiology, Immunology, and Molecular Genetics
The innate arm of the immune system provides the first line of defense against invading pathogens. In the context of innate antiviral immunity, the induction of type I interferon pathway, characterized by activation of the transcription factors IRF3 and NF?B, is critical in limiting viral replication and spread. Although the broad mechanisms of IFN signaling and effector function are established, the mechanisms by which the TBK1/IKKi kinases are activated to signal to IRF3 are not really well understood. Aberrant activation of TBK1 has been demonstrated in oncogenic KRAS dependent tumors. Thus, identification and targeting of key TBK1 activating kinases could potentially provide a therapeutic target to combat select tumors. Here, we identified salt inducible kinase 2 (SIK2) as a critical regulator of the IRF3 transcription-mediated antiviral response. Our findings suggest that SIK2 plays important roles in IRF3 activation by operating downstream of TBK1 and provide new insights into the molecular mechanisms of cellular antiviral response.