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PXD042004

PXD042004 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTRIM21 enhances bortezomib sensitivity in multiple myeloma by halting pro-survival autophagy
DescriptionBortezomib (bort) is an effective therapeutic agent for multiple myeloma (MM) patients; however, the majority of patients develop drug resistance. Autophagy, a highly conserved process that recycles cytosol or entire organelles via lysosomal activity, is essential for the survival, homeostasis and drug resistance in MM. Growing evidence has highlighted that E3 ligase tripartite motif-containing protein 21 (TRIM21) not only interacts with multiple autophagy regulators but also participates in drug resistance in various cancers. However, to date, the direct substrates and additional roles of TRIM21 in MM remain unexplored. In this study, we demonstrated that low TRIM21 expression is a factor for relapse in MM. TRIM21 knockdown (KD) made MM cells more resistant to bort, while TRIM21 overexpression (OE) resulted in increased MM sensitivity to bort. Proteomic and phospho-proteomic studies of TRIM21 KD MM cells showed that bort resistance was associated with increased oxidative stress and elevated pro-survival autophagy. Our results provided that TRIM21 KD MM cell lines induced pro-survival autophagy after bort treatment, and suppressing autophagy by 3-methyladenine treatment or by the short hairpin RNA of ATG5 restored bort sensitivity. Indeed, autophagy-related gene 5 (ATG5) expression was increased and decreased by TRIM21 KD and OE, respectively. TRIM21 affected autophagy by ubiquitinating ATG5 through K48 for proteasomal degradation. Importantly, we confirmed that TRIM21 could potentiate the anti-myeloma effect of bort through in vitro and in vivo experiments. Overall, our findings define the key role of TRIM21 in MM bort resistance and provide a foundation for a novel targeted therapeutic approaches.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_09:09:33.093.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJing Chen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitinylated lysine
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-05 01:13:59ID requested
12023-10-24 12:38:10announced
22023-11-14 09:09:41announced2023-11-14: Updated project metadata.
Publication List
Chen J, Cao W, Huang X, Chen Q, Ye S, Qu J, Liu Y, Guo X, Yao S, Zhang E, He J, Li A, Yang L, Cai Z, TRIM21 enhances bortezomib sensitivity in multiple myeloma by halting prosurvival autophagy. Blood Adv, 7(19):5752-5770(2023) [pubmed]
Keyword List
submitter keyword: TRIM21;multiple myeloma;bortezomib
Contact List
Jing Chen
contact affiliationBone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
contact email11418106@zju.edu.cn
lab head
Jing Chen
contact affiliationBone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine
contact email11418106@zju.edu.cn
dataset submitter
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