PXD037309 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma |
Description | Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n=4146), we observe no correlation between serum Ig levels and patient survival, while amount of intracellular Ig has a strong predictive effect. Focused CRISPR screen, transcriptional and proteomic analysis identify deubiquitinase OTUD1 as a critical mediator of Ig synthesis, proteasome inhibitor sensitivity and tumour burden in MM. Mechanistically, OTUD1 deubiquitinates peroxiredoxin 4 (PRDX4), protecting it from endoplasmic reticulum (ER)-associated degradation. In turn, PRDX4 facilitates the synthesis of Ig which coincides with the accumulation of unfolded proteins and higher ER stress. The elevated load on proteasome ultimately potentiates myeloma response to proteasome inhibitors providing a window for a rational therapy. Collectively, our findings support the significance of the Ig production machinery as a yet unappreciated biomarker and target in the combinatory treatment of MM patients. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:38:27.822.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD037309 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Karel Harant |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-10-12 07:02:11 | ID requested | |
1 | 2023-03-10 23:29:57 | announced | |
⏵ 2 | 2023-11-14 08:38:28 | announced | 2023-11-14: Updated project metadata. |
Publication List
10.6019/PXD037309; |
Vdovin A, Jelinek T, Zihala D, Sevcikova T, Durech M, Sahinbegovic H, Snaurova R, Radhakrishnan D, Turi M, Chyra Z, Popkova T, Venglar O, Hrdinka M, Hajek R, Simicek M, The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma. Nat Commun, 13(1):6820(2022) [pubmed] |
Keyword List
submitter keyword: Multiple myeloma, deubiquitinase OTUD1 |
Contact List
Michal Simicek 1,2,3,* |
contact affiliation | 1 Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Syllabova 19, 703 00, Czech Republic 2 Department of Hematooncology, University Hospital Ostrava, Ostrava, 17. listopadu 1790/5, 708 00, Czech Republic 3 Faculty of Science, University of Ostrava, Ostrava, 30. dubna 22, 701 03, Czech Republic * Correspondence and requests for materials should be addressed to M.S. (email: michal.simicek@fno.cz). |
contact email | michal.simicek@fno.cz |
lab head | |
Karel Harant |
contact affiliation | Charles University |
contact email | harant@natur.cuni.cz |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037309
- Label: PRIDE project
- Name: The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma