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PXD046953

PXD046953 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMidnolin stimulates proteasome activity necessary for lymphopoiesis and B cell cancer growth
DescriptionWe identified the essential gene encoding midnolin in a genetic screen in which multiple Midn alleles caused reductions in peripheral B cells and T cell-independent antibody responses. Causation was confirmed in mice with targeted deletion of 4 of 6 MIDN protein isoforms. MIDN augmented proteasome activity in lymphocytes but few other cell types. By cryo-electron microscopy we showed that MIDN binds directly to the 26S proteasome. MIDN-deficient B cells displayed aberrant activation of the IRE-1/XBP-1 pathway of the unfolded protein response. Partial or complete MIDN deficiency suppressed B lymphoproliferation in three models of B cell malignancies. Thus, MIDN is required for proteasome activity in support of lymphopoiesis and malignant B cell proliferation over a broad range of differentiation states. Targeting MIDN in B cell malignancies may avoid off-tumor toxicities caused by proteasome inhibition throughout the body.
HostingRepositoryMassIVE
AnnounceDate2024-04-11
AnnouncementXMLSubmission_2024-04-11_07:14:00.669.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJames Moresco
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-14 06:56:45ID requested
12024-04-11 07:14:01announced
Publication List
no publication
Keyword List
submitter keyword: Midnolin, proteasome, lymphopoiesis, B cell cancer
Contact List
Bruce Beutler
contact affiliationUT Southwestern Medical Center
contact emailBruce.Beutler@utsouthwestern.edu
lab head
James Moresco
contact affiliationUT Southwestern
contact emailjames.moresco@utsouthwestern.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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