PXD066445-1

PXD066445 is an original dataset announced via ProteomeXchange.

Title	USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination
Description	Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy driven by genetic and epigenetic alterations, where super-enhancers (SEs) play key oncogenic roles, representing promising therapeutic targets in AML. Through H3K27ac ChIP-seq profiling of 7 AML cell lines and 13 primary samples, we identified USP20 as the deubiquitinase that most frequently associated with super-enhancers. Public database analysis confirmed USP20 overexpression in AML and its correlation with adverse prognosis. Genetic knockdown of USP20 via shRNA significantly induced apoptosis and suppressed proliferation in AML cells in vitro, while in vivo depletion of USP20 attenuated leukemia development and improved overall survival. AS1517499, a novel USP20 inhibitor identified via virtual screening, recapitulated these anti-leukemic effects in vitro and in vivo with low toxicity. Mechanistically, USP20 interacts with CTNNB1 and stabilizes the CTNNB1 protein via deubiquitination. CUT&Tag analysis indicated that USP20 co-localizes with CTNNB1 on the genome, where they jointly regulate target genes in AML. Collectively, our study identified USP20 as a super-enhancer-regulated oncogene maintaining AML cell survival and proliferation through CTNNB1 stabilization. Pharmacologic targeting of USP20 with AS1517499 presents a promising therapeutic strategy targeting the SE-USP20- CTNNB1 axis.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_03:41:35.539.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fang Fang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-23 01:34:11	ID requested
⏵ 1	2026-03-16 03:41:36	announced

10.7150/ijbs.122898;

Cheng J, Fang F, Li Z, Wang J, Cai L, Xu L, Tao Y, Yu J, Li G, Zhang Z, Cui Z, Yang Y, Li T, Wu D, Li X, Ding Y, Zhai Z, Gu M, Li X, Wu X, Yang P, Shi C, Bai H, Wang X, Han L, Shi L, Li J, Pan J, USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination. Int J Biol Sci, 22(5):2665-2686(2026) [pubmed]

submitter keyword: USP20

Super-enhancer

AML

CTNNB1

AS1517499

Jia Cheng
contact affiliation	Children's Hospital of Soochow University, Suzhou
contact email	tsspc111@163.com
lab head
Fang Fang
contact affiliation	Children's Hospital of Soochow University
contact email	baseff@sina.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD066445

PRIDE project URI

• PRIDE
  1. PXD066445
     1. Label: PRIDE project
     2. Name: USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination