A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death.

A small-molecule bivalent glue activates cell death in diffuse large B cell lymphoma by linking lysine acetyltransferases to oncogenic pathways, achieving targeted epigenetic reprogramming.

• Why it matters: Inducing specific death of cancer cells is essential to prevent relapse, yet current therapies lack precise mechanisms to selectively trigger apoptosis in malignant cells. Understanding how to harness oncogenic drivers for therapeutic benefit remains a critical challenge.
• What they did: Researchers designed lysine acetyltransferase-based TCIPs (KAT-TCIPs) that chemically induce proximity between p300/CBP and BCL6, reprogramming the epigenome to activate apoptosis, supported by structural analysis of the p300-BCL6 complex.
• The result: This approach demonstrates that oncogenic drivers can be exploited to selectively induce cell death, with different transcriptional activators producing distinct genomic responses, opening avenues for tailored cancer therapies.