PXD037309

PXD037309 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: Multiple myeloma, deubiquitinase OTUD1

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

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PRIDE project URI

• PRIDE
  1. PXD037309
     1. Label: PRIDE project
     2. Name: The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma