PXD045576

PXD045576 is an original dataset announced via ProteomeXchange.

Title	CCT3 drives sorafenib resistance by inhibiting TFRC-mediated iron uptake in HCC
Description	Sorafenib is commonly utilized in the management of advanced hepatocellular carcinoma (HCC). However, its efficacy in extending patients' survival is hindered by the development of drug resistance. By employing protein posttranslational modification (PTM) omics, including acetylome, phosphoproteome, and ubiquitinome, in conjunction with genome-wide CRISPR/Cas9 knockout library screening, we have successfully identified chaperonin containing TCP1 subunit 3 (CCT3) as a key factor contributing to sorafenib resistance. Furthermore, we observed a reduction in the ubiquitination of CCT3 at lysine 21 (K21) subsequent to sorafenib treatment. This study provides evidence that CCT3 hinders the recycling of transferrin receptor protein 1 (TFRC) by interacting with alpha-actinin-4 (ACTN4), which is influenced by K6-linked ubiquitination on K21. Depleting CCT3 increased the susceptibility of cells to sorafenib-induced ferroptosis, while reintroducing CCT3 through transfection restored resistance to ferroptosis. Additionally, impairing ACTN4 or TFRC depletion compromised CCT3's ability to inhibit sorafenib-induced ferroptosis. In summary, targeting CCT3 presents a potential strategy for overcoming sorafenib resistance in HCC.
HostingRepository	iProX
AnnounceDate	2023-09-21
AnnouncementXML	Submission_2024-01-03_20:03:58.664.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Feiayang Ji
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	acetylated residue; phosphorylated residue; ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive HF-X; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-21 19:12:14	ID requested
⏵ 1	2024-01-03 20:03:59	announced

Dataset with its publication pending

submitter keyword: Sorafenib, HCC, CCT3, Ferroptosis, ACTN4

Feiyang Ji
contact affiliation	Zhejiang University
contact email	feiyangji@zju.edu.cn
lab head
Feiayang Ji
contact affiliation	Zhejiang University
contact email	feiyangji@zju.edu.cn
dataset submitter

iProX dataset URI