PXD062446-1
PXD062446 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Blocking TRIM47-mediated HNF4α degradation Suppress Hepatocellular Carcinoma Progression |
Description | Previous studies have highlighted the downregulation of hepatocyte nuclear factor 4α (HNF4α) as a critical event in the pathogenesis of HCC. However, the mechanism of its degradation in HCC remains unclear. Tripartite motif 47 (TRIM47), a typical E3 ubiquitin ligase of the TRIM family, implicates various tumors, yet its specific role in HCC progression is not fully elucidated. In this study, HNF4α was identified as a potential target of TRIM47 by using co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis. TRIM47 facilitates the degradation of HNF4α by mediating K48-linked ubiquitination at lysine 470. Abrogation of HNF4α ubiquitination attenuated the promoting effect of TRIM47 on HCC malignancy. Molecular docking studies and Co-IP experiments revealed that K342, W349, and E353 of HNF4α, along with K534 and K600 of TRIM47 are crucial for their interaction. A small molecular, CZ-2401, was selected as a potent inhibitor of the TRIM47-HNF4α interaction through virtual screening and pharmacological activity validation. CZ-2401 effectively stabilizes HNF4α protein in HCC cells and ameliorates TRIM47-driven HCC progression in vivo. Taking together, our research elucidates that targeting TRIM47-HNF4α interaction is a potential therapeutic strategy for HCC, and identifies CZ-2401 as a potent inhibitor of HNF4α degradation and a promising candidate for HCC therapy. |
HostingRepository | iProX |
AnnounceDate | 2025-04-01 |
AnnouncementXML | Submission_2025-06-03_20:10:28.056.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jing Gao |
SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2025-04-01 01:12:27 | ID requested | |
⏵ 1 | 2025-06-03 20:10:28 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: TRIM47, HNF4α, Ubiquitination, CZ-2401, Hepatocellular carcinoma |
Contact List
Hu Zhou | |
---|---|
contact affiliation | Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
contact email | zhouhu@simm.ac.cn |
lab head | |
Jing Gao | |
contact affiliation | Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
contact email | jinggao@simm.ac.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |