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Optineurin regulates the interferon response in a cell cycle-dependent manner
Pierre Génin1, Frédérique Cuvelier1, Sandrine Lambin1
1Laboratoire de Signalisation et Pathogenèse, CNRS UMR3691, Institut Pasteur, Paris, France.
Plos Pathogens
|April 30, 2015
Summary
Optineurin (Optn) dampens antiviral immunity by inhibiting TANK-binding Kinase 1 (TBK1). This regulation fails during mitosis, increasing TBK1 activity and interferon production for a preventive antiviral response.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Innate immunity recognizes viral invasion via cytosolic signaling pathways.
- Activation of IRF3 and NF-κB transcription factors induces type I interferon.
- TANK-binding Kinase 1 (TBK1) phosphorylates and activates IRF3.
Purpose of the Study:
- To investigate the role of Optineurin (Optn) in regulating the antiviral innate immune response.
- To elucidate the mechanism by which Optn influences TBK1 activity.
- To understand the impact of cell division on this regulatory process.
Main Methods:
- Investigated the interaction between Optineurin (Optn), CYLD, and TANK-binding Kinase 1 (TBK1).
- Analyzed the subcellular localization of CYLD and Optn during the cell cycle.
- Assessed TBK1 activity and interferon production at different cell cycle phases.
Main Results:
- Optineurin (Optn) targets CYLD to TBK1, inhibiting its enzymatic activity and dampening antiviral responses.
- This inhibitory mechanism is abolished during the G2/M phase due to nuclear translocation of CYLD and Optn.
- TBK1 activity, phosphorylation, and mitochondrial relocalization increase during mitosis, leading to enhanced interferon production.
Conclusions:
- Optineurin (Optn) plays a crucial role in regulating the antiviral innate immune response.
- The regulation of TBK1 by Optn is cell cycle-dependent, with impaired inhibition during mitosis.
- Enhanced interferon production during mitosis, mediated by Optn, suggests a role in preventive antiviral defense.
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