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Researchers from Nuffield Department of Medicine, Department of Biochemistry and CAMS Oxford Institute uncover how BIRC6 (a giant ubiquitin ligase) protects cells from death and how this can be antagonised.

BIRC6 - a giant ubiquitin ligase and essential regulator of cell death is antagonised by SMAC
BIRC6 (blue/grey) - a giant ubiquitin ligase and essential regulator of cell death is antagonised by SMAC (yellow)

Cell survival and death are a finely balanced act, important for normal development of multicellular organisms. Many cancer cells switch off cell death mechanisms and upregulate proteins that normally prevent unwanted cell death thus ensuring their survival. Inhibitor of Apoptosis Proteins (IAPs) are a family of proteins that prevent untimely cell death. 

The research, published in Science, uses single particle cryo-EM and detailed biochemical analyses to uncover how the giant IAP BIRC6 keeps cells alive through counteracting the function of caspases – enzymes that execute cell death. Furthermore, the study reveals how this cell guardian function of BIRC6 is antagonised by SMAC once cells become committed to dying. These findings pave the way for development of small molecules targeting BIRC6 in cancer cells to restore cell death.

Read the full story on the Department of Biochemistry website

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