Related Experiment Video

Updated: Aug 6, 2026

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
05:58

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells

Published on: February 24, 2026

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

Meredith N Nix1, Sai Gourisankar2, Kevin J Bowman3

  • 1Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA; Department of Chemistry, Stanford University, Stanford, CA, USA.

Cell
|July 20, 2026
PubMed

Insights

Scientists developed novel small-molecule therapies called KAT-TCIPs to target diffuse large B cell lymphoma. These therapies reprogram the epigenome, activating cell death pathways and offering a new approach for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Chemical Biology

Background:

  • Developing targeted cancer therapies that induce specific cancer cell death is crucial for preventing relapse.
  • Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, necessitating effective treatment strategies.

Purpose of the Study:

  • To provide the mechanistic basis for a small-molecule approach using chemically induced proximity (CIP) to kill DLBCL cells.
  • To develop novel transcriptional/epigenetic chemical inducers of proximity (TCIPs) that leverage lysine acetyltransferase (KAT) activity.

Main Methods:

  • Development of KAT-based TCIPs (KAT-TCIPs) designed to redirect p300/CREB-binding protein (CBP) activity.
  • Utilizing the crystal structure of the chemically induced p300-BCL6 complex to understand potency and selectivity.
  • Investigating the genomic responses of TCIPs recruiting different transcriptional activators (p300, BRD4, CDK9).

Main Results:

  • The lead KAT-TCIP reprograms the epigenome to initiate apoptosis in DLBCL cells.
  • The study revealed how protein-protein interactions can be exploited for therapeutic effect.
  • Distinct genomic responses were observed based on the recruited transcriptional activator, suggesting specialized therapeutic applications.

Conclusions:

  • Oncogenic drivers can be co-opted to activate robust cell death pathways.
  • KAT-TCIPs represent a promising small-molecule strategy for targeting DLBCL by inducing specific cancer cell death.
  • The mechanism provides a foundation for developing tailored TCIP-based therapies for various cancers.
Keywords:
BCL6CIPDLBCLchemically induced proximitylymphomalysine acetyltransferasestranscription

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