Evidence map›Paper›PMID 40166243›Full record

ArticlebioRxiv : the preprint server for biology2025

A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death.

Meredith N Nix, Sai Gourisankar, Roman C Sarott, Brendan G Dwyer, Sabin A Nettles, Michael M Martinez, Hind Abuzaid, Haopeng Yang, Yanlan Wang, Juste M Simanauskaite and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Meredith N NixDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0009-0007-0501-8452
Sai GourisankarDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0132-8086
Roman C SarottDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8789-6150
Brendan G DwyerDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8593-4184
Sabin A NettlesDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-1913-9016
Michael M MartinezDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
Hind AbuzaidDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-5454-7672
Haopeng YangDepartment of Lymphoma- & Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-3870-2679
Yanlan WangDepartment of Pathology, Stanford University, Stanford, CA, USA.
Juste M SimanauskaiteDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0009-0009-1385-2599
Bryan A RomeroDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
Hannah M JonesDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
Andrey KrokhotinDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0009-0006-4435-3213
Tara N LowensohnDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3195-1135
Lei ChenDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Cara LowDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
Mark M DavisDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Daniel FernandezMacromolecular Structure, Nucleus at Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Tinghu ZhangDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-1028-8020
Michael R GreenDepartment of Lymphoma- & Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0001-6309-9472
Stephen M HinshawDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4215-5206
Nathanael S GrayDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5354-7403
Gerald R CrabtreeDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-9685-7911

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Ritimukta Sarangi · 2020 to 2026
$43.3M
ATP-Dependent Chromatin Remodeling in Human MalignancyR01CA163915 · NCI · STANFORD UNIVERSITY · PI Gerald R. Crabtree · 2012 to 2026
$5.4M
Identifying/Targeting Mechanisms of Lymphomagenesis Driven by CREBBP InactivationR01CA201380 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Richard Green · 2016 to 2026
$3.5M
HIJACKING CANCER DRIVERS TO ACTIVATE PROAPOPTOTIC GENES IN DLBCLR01CA276167 · NCI · STANFORD UNIVERSITY · PI Gerald R. Crabtree, NATHANAEL Schiander GRAY · 2023 to 2026
$2.2M
Small molecule regulation of endogenous transcription factors for circuit-specific neuromodulationRF1MH126720 · NIMH · STANFORD UNIVERSITY · PI CRABTREE, GERALD R. · 2021 to 2021
$1.3M
500 MHz NMR Spectrometer System with High Sensitivity Cryoprobe and Automated Sample Changer for Biochemical ResearchS10OD028697 · OD · STANFORD UNIVERSITY · PI BURNS, NOAH ZACHARY · 2020 to 2020
$709k
Rewiring fusion oncogenes to activate apoptosisK99CA296700 · NCI · STANFORD UNIVERSITY · PI Sai Gourisankar · 2025 to 2026
$271k
NCI NIH HHS K99 CA296700NCI NIH HHS R01 CA163915NCI NIH HHS R01 CA201380NCI NIH HHS R01 CA276167NIGMS NIH HHS P30 GM133894NIH HHS S10 OD028697NIMH NIH HHS RF1 MH126720
6 · The paper itself

Abstract

Developing cancer therapies that induce robust death of the malignant cell is critical to prevent relapse. Highly effective strategies, such as immunotherapy, exemplify this observation. Here we provide the structural and molecular underpinnings for an approach that leverages chemical induced proximity to produce specific cell killing of diffuse large B cell lymphoma, the most common non-Hodgkin's lymphoma. We develop KAT-TCIPs (lysine acetyltransferase transcriptional/epigenetic chemical inducers of proximity) that redirect p300 and CBP to activate programmed cell death genes normally repressed by the oncogenic driver, BCL6. Acute treatment rapidly reprograms the epigenome to initiate apoptosis and repress c-MYC. The crystal structure of the chemically induced p300-BCL6 complex reveals how chance interactions between the two proteins can be systematically exploited to produce the exquisite potency and selectivity of KAT-TCIPs. Thus, the malignant function of an oncogenic driver can be co-opted to activate robust cell death, with implications for precision epigenetic therapies.

Indexed as

induced proximitylymphomalysine acetyltransferasestranscription

Identifiers

PMID40166243
PMCPMC11956963

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.