Integration of innate immune signaling by caspase-8 cleavage of N4BP1

A new target found for caspase-8

31 January 2021

A missing piece in the puzzle about the role that the protein caspase-8 plays in regulating immune responses has been found.

Caspase-8 is an enzyme that slices target proteins in two. Its activation can cause multiple responses, including inducing one form of cell death while suppressing another. It also promotes the expression of genes that lead to inflammation. But it hasn’t been clear how one protein can have such diverse effects.

Now, a team that included researchers at the Roche subsidiary Genentech has found that caspase-8 acts on the protein N4BP1 — a previously unknown target of the enzyme. They found that N4BP1 represses the production of small proteins known as cytokines that are active in the initial immune response to pathogens.

This finding illuminates how caspase-8 drives inflammatory responses in mammalian cells. It also explains why mutations to the genes that code for caspase-8 or its adaptor result in lowered immunity.

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References

1. Nature 587, 275–280 (2020). doi: 10.1038/s41586-020-2796-5