PXD062446

PXD062446 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-01 01:12:27	ID requested
⏵ 1	2025-06-03 20:10:28	announced

Dataset with its publication pending

submitter keyword: TRIM47, HNF4α, Ubiquitination, CZ-2401, Hepatocellular carcinoma

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

iProX dataset URI