PXD058540

PXD058540 is an original dataset announced via ProteomeXchange.

Title	BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling
Description	Arginine methylation is a common posttranslational modification that is catalyzed by a family of protein arginine methyltransferases. Recognition of methylarginine marks by effector proteins (“readers”) is a critical link between arginine methylation and various cellular processes. We recently identified methylation of AKT1 at Arg391 by PRMT5, but the reader for this methylation has yet to be characterized. Here, we show that BRD9, a reader of acetylated lysine, unexpectedly recognizes Arg391-methylated AKT1 through an aromatic cage in its bromodomain. Disrupting the methylarginine reader function of BRD9 suppresses AKT activation and tumorigenesis. RNA-sequencing data shows that BRD9 and AKT co-regulate a hallmark transcriptional program in part through EZH2-mediated H3K27 trimethylation. Lastly, we find that inhibitors of BRD9 and EZH2 display synergistic effects on inhibition of cell viability and tumor growth. Together, our study demonstrates that BRD9 serves as a methylarginine reader to promote AKT-EZH2 oncogenic signaling and combined inhibition of BRD9 and EZH2 is a potential strategy for cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2025-03-18
AnnouncementXML	Submission_2025-03-18_08:10:40.146.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-03 11:06:52	ID requested
⏵ 1	2025-03-18 08:10:40	announced

Dataset with its publication pending

submitter keyword: methylarginine, AKT-EZH2 signaling,BRD9

Wenjian Gan
contact affiliation	Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC29425, USA
contact email	ganw@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058540
     1. Label: PRIDE project
     2. Name: BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling