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FADD is recruited to activated STING oligomers initiating caspase mediated NF-κB activation in Drosophila melanogaster

ABSTRACT: STING is an evolutionarily conserved key regulator of innate immunity. In mammals, STING activates two distinct signaling pathways, the IRF3 and the NF-κB pathways, which act in conjunction to drive antiviral immunity. While the molecular mechanism of STING-mediated IRF3 activation has been untangled by extensive work during the last decade, how STING activates NF-κB signaling remains poorly understood. The versatile FADD/Caspase 8 axis is widely used in various immune signaling pathways throughout the animal kingdom and here we show that this axis participates downstream of STING in the activation of the Drosophila NF-kB like transcription factor Relish. We provide a detailed structural model illustrating how FADD interacts with two separate STING dimers in the activated oligomerized form of STING, thus providing a molecular explanation for the signal-dependent recruitment of FADD. In the classic IMD signaling pathway, FADD interacts with IMD in a structural distinct but functional related manner, highlighting how the two pathways differentially utilize the adapter FADD.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Cell Culture

SUBMITTER: Katarzyna Kjøge

LAB HEAD: Rune Hartmann

PROVIDER: PXD054811 | Pride | 2026-04-09

REPOSITORIES: Pride

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			Action	DRS
	20231219_KK_EGFP_1.raw	Raw
	20231219_KK_EGFP_2.raw	Raw
	20231219_KK_EGFP_3.raw	Raw
	20231219_KK_Sting_1.raw	Raw
	20231219_KK_Sting_2.raw	Raw

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