PXD046714 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion |
| Description | ZHX3, which encodes for a transcriptional repressor, is associated with fasting blood glucose (FBG) levels and increased type 2 diabetes (T2D) risk but its role in cell types involved in glucose metabolism is not well understood. Here, we show that the deletion of ZHX3 in the human pancreatic β cell line EndoC-βH1 did not impair glucose-stimulated insulin secretion (GSIS) nor perturb its transcriptome. On the other hand, we found that ZHX3 represses the expression of gluconeogenic genes PCK1 and G6PC1 in the human hepatoma line HepG2. Transcriptomic analysis of ZHX3-deficient HepG2 cells revealed that the uric acid transporter gene SLC17A1 was upregulated, which consequentially led to increased uric acid secretion. High levels of uric acid could then impair GSIS in EndoC-βH1 cells. Subsequently, in-depth co-immunoprecipitation followed by mass spectrometry analysis of ZHX3 in HepG2 cells identified transcription factor CEBPB as its binding partner, required to repress the transcription of PCK1, G6PC1 and partially SLC17A1 in HepG2 cells. Overall, our study uncovered the role of ZHX3 in regulating glucose metabolism in hepatocytes, thereby influencing FBG levels and its association with T2D risk. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-04-27 |
| AnnouncementXML | Submission_2026-04-26_17:06:33.849.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Suat Peng Neo |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2023-11-06 18:48:04 | ID requested | |
| ⏵ 1 | 2026-04-26 17:06:34 | announced | |
Publication List
| 10.1093/pnasnexus/pgae568; |
| Tan WX, Lim LY, Afsha N, Chan GME, Ching C, Oguz G, Neo SP, Mohamed Ali S, Ramasamy A, Gunaratne J, Hunziker W, Khoo CM, Teo AKK, ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion. PNAS Nexus, 4(2):pgae568(2025) [pubmed] |
Keyword List
| submitter keyword: beta cell,Type 2 diabetes |
| ZHX3 |
| gluconeogenesis |
| fasting blood glucose |
| hepatic glucose production |
| liver |
| hepatocytes |
| uric acid |
| SLC17A1 |
Contact List
| Jayantha Gunaratne |
|---|
| contact affiliation | Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore |
| contact email | jayanthag@imcb.a-star.edu.sg |
| lab head | |
| Suat Peng Neo |
|---|
| contact affiliation | Institute of Molecular and Cell Biology (ASTAR) |
| contact email | neosp@imcb.a-star.edu.sg |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046714
- Label: PRIDE project
- Name: ZHX3 interacts with CEBPB to repress hepatic gluconeogenic gene expression and uric acid secretion
