Evidence map›Paper›PMID 40279411›Full record

ArticleScience advances2025

BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling.

Shasha Yin, Charles Brobbey, Lauren E Ball, Tianmin Fu, Daniel J Sprague, Wenjian Gan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Shasha YinDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0001-9443-6291
Charles BrobbeyDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Lauren E BallDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0001-6780-1679
Tianmin FuDepartment of Biological Chemistry and Pharmacology, Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0002-6281-1752
Daniel J SpragueDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0002-0709-3284
Wenjian GanDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0001-7599-5020

Funding

Regulatory Mechanisms of Arginine MethylationR35GM146749 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Wenjian Gan · 2022 to 2026
$1.9M
Characterizing and targeting PRMT5 in autophagy for cancer treatmentR01CA266522 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Wenjian Gan · 2023 to 2026
$1.4M
NCI NIH HHS R01 CA266522NIGMS NIH HHS R35 GM146749
6 · The paper itself

Abstract

Recognition of methylarginine marks by effector proteins ("readers") is a critical link between arginine methylation and various cellular processes. Recently, we identified methylation of AKT1 at arginine-391 (R391), but the reader for this methylation has yet to be characterized. Here, we show that bromodomain-containing protein 9 (BRD9), a reader of acetylated lysine, unexpectedly recognizes methylated R391 of AKT1 through an aromatic cage in its bromodomain. Disrupting the methylarginine reader function of BRD9 suppresses AKT activation and tumorigenesis. RNA sequencing data show that BRD9 and AKT coregulate a hallmark transcriptional program in part through enhancer of zeste homolog 2 (EZH2)-mediated methylation of histone-3 lysine-27. We also find that inhibitors of BRD9 and EZH2 display synergistic effects on suppression of cell proliferation and tumor growth. Collectively, our study reveals a previously unknown function of BRD9 and a potential therapeutic strategy for cancer treatment by combining BRD9 and EZH2 inhibitors.

Indexed as

ArginineEnhancer of Zeste Homolog 2 ProteinProto-Oncogene Proteins c-aktSignal TransductionTranscription FactorsAnimalsBromodomain Containing ProteinsCell Line, TumorCell ProliferationHistonesHumansMethylationMiceArginineBRD9 protein, humanBromodomain Containing ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesProto-Oncogene Proteins c-aktTranscription Factors

Identifiers

PMID40279411
PMCPMC12024519

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

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 Socratic graph.