Caspase-3 cleaves CYLD to restrict interferon signaling during mitochondrial apoptosis.

Caspase-3 cleaves CYLD at a novel site to limit interferon signaling during mitochondrial apoptosis, reducing inflammation and promoting immune silence.

• Why it matters: Understanding how apoptosis suppresses immune activation is crucial for insights into immune regulation and inflammatory diseases. The mechanisms by which caspases control inflammatory signaling during cell death remain unclear.
• What they did: The study used a combination of biochemical and genetic approaches, including knock-in cells with CASP3-resistant CYLD, to investigate CYLD cleavage and its effects on interferon signaling during apoptosis.
• The result: Cleavage of CYLD by CASP3 restricts interferon production and cell death, revealing a proteolytic code that balances inflammation and immune silence in programmed cell death.