PXD066624

PXD066624 is an original dataset announced via ProteomeXchange.

Title	ZNF184 Negatively Regulates HR Repair and Predicts Poor Prognosis in Acute Lymphoblastic Leukemia
Description	Zinc finger proteins (ZNFs) are increasingly recognized as regulators of oncogenic transcriptional networks and DNA damage responses. Through integrative analysis of bulk and single-cell RNA sequencing data, we identified a conserved set of seven ZNF genes, including ZNF184, that are upregulated in acute lymphoblastic leukemia (ALL) and exhibit dynamic expression patterns linked to disease progression. Among these, ZNF184 uniquely localized to DNA double-strand breaks (DSBs) in a zinc finger domain-dependent manner. Functional analyses revealed that ZNF184 suppresses homologous recombination (HR)-mediated DNA repair by impeding BRCA1 recruitment, leading to accumulation of DNA damage. ZNF184 expression was elevated in primary ALL samples and associated with increased γH2AX levels and inferior overall survival in ALL patients. Loss of ZNF184 restored HR efficiency, reduced DNA damage burden, and enhanced genome stability, while re-expression re-sensitized cells to DNA-damaging agents. Mechanistically, ZNF184 directly interacted with TRIM28 and facilitated its recruitment to DSBs, modulating TRIM28 phosphorylation and chromatin remodeling through the HP1/SUV39H1 complex. ZNF184 expression conferred heightened sensitivity to PARP inhibition and synergized with genotoxic chemotherapy in both cell lines and patient-derived ALL cells. These findings identify ZNF184 as a key modulator of DSB repair and a predictive biomarker for therapeutic strategies targeting HR-deficient ALL.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:19:37.608.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD066624
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Byung-gyu kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-27 17:18:41	ID requested
⏵ 1	2026-06-07 16:19:38	announced

Hwang WC, Ju HY, Park K, Kwon EJ, Seo ES, Chung Y, Kim BG, Myung K, Lim DM, Kim YH, Yoo KH, Kim H, ZNF184 negatively regulates HR repair and predicts poor prognosis in acute lymphoblastic leukemia. Nucleic Acids Res, 54(10):(2026) [pubmed]

10.6019/PXD066624;

10.1093/nar/gkag486;

submitter keyword: Negative regulator,LC-MS/MS,Acute lymphoblastic leukemia, Zinc finger proteins, Homologous recombination repair, TRIM28

Hongtae Kim
contact affiliation	Department of Biological Sciences, Ulsan National Institute of Science and Technology,50 UNIST-gil, Ulju-gun, Ulsan 44919, Republic of Korea
contact email	khtcat@unist.ac.kr
lab head
Byung-gyu kim
contact affiliation	Center for genomic integrity (CGI), Institute of basic science (IBS), UNIST, Ulsan, 44919, Republic of Korea
contact email	goldenlion@ibs.re.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066624
     1. Label: PRIDE project
     2. Name: ZNF184 Negatively Regulates HR Repair and Predicts Poor Prognosis in Acute Lymphoblastic Leukemia