MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v06/MSV000093397/primary200OKBruce Beutlerhttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=cd804a1b8fc4420185efe986c36d6b2fBruce.Beutler@utsouthwestern.eduMassIVE26MS:1002864 - No post-translational-modifications are included in the identified peptides of this datasetProteomicsQ Exactive HFMus Musculus (ncbitaxon:10090)UT Southwestern Medical CenterCryomicroscopies, B Cells, Materials, Activity, Laboratory, Bursa-Dependent Lymphocytes, Mus domesticus, B cell, Splice Variants, 26S protease, CASP-14, T-Lymphocyte, B-cell receptor complex, Tumor, Protein Splice, Protein Response, House Mouse, dmTAF[[II]]230, T Lymphocyte, Multicatalytic Endopeptidase Complex, animal, immature T cell, Ire, XBP-1, Protein Splice Variant, TFIID TAF250, Macropain, cel, membrane bound, T-Cells, T, Swiss Mice, Protein Isoform, Proteasome Endopeptidase, 20S Proteasome, genetic, D11Ertd39e, T Cells, XBP2, B lymphocyte, B-cell proliferation, Allele, 26S proteasome, Lymphoid, Cryoelectron, Malignancies, B-lymphocyte receptor complex, dIRE1, Thymus Dependent Lymphocytes, Tumors, dTAF[[II]]230, Proteinase, Endopeptidase Complex, wide/broad, 26 S proteasome complex, aberrant, B Lymphocytes, B lymphocyte proliferation, familial, mouse, TAF200, Cryo-electron, Isoform, TAFII-250, antibodies, TAF250/230, Ingensin, TAFII250, Benign, T-Cell, Cryomicroscopy, Mini-ICE, Electron Cryomicroscopy, Responses, Genetic Materials, Lymphoid Cell, Cryoelectron Microscopies, Genetic Material, activation, proteasome, Mus musculus, Koerper., T-cell, whole organism, Caspase-14 subunit p10, mice, Thymus-Dependent, Swiss Mouse, Benign Neoplasms, INSDC_feature:gene, Caspase-14 subunit p19, Electron, T-lymphocyte, MICE, CG17603, Ire-1, TAF[[II]], Thymus-Dependent Lymphocyte, domesticus, Malignant Neoplasms, immunoglobulin, wide, T cell, B cell receptor accessory molecule complex, Taf250, Material, B-Lymphocyte, SR3-5, Cells, B lymphocyte receptor complex, Cistron, inherited genetic, T Cell, Mouse, Microscopy, other neoplasm, ire-1, TAF230, 3.4.22.-, atypia, Allelomorphs, d230, Thymus-Dependent Lymphocytes, Neoplasms, Benign Neoplasm, Gene, midn, mini-ICE, dTAFII250, broad, EfW1, Malignant, Cryo-electron Microscopy, antibody, Multicatalytic Proteinase, BCR complex, House, dmTAF1, Taf230, Variant, Mus musculus domesticus, atypical, Isoforms, immunoglobulin complex, Mice, TREB5, Splice Variant, Tax-responsive element-binding protein 5, TAF250, DmelCG4583, Taf200, B-cell, dTAF[[II]]250, Genetic, Unfolded Protein, Malignancy, Swiss, cell, Complex, Taf1p, Protein Splice Variants, IRE1, Unfolded, Allelomorph, Neoplasias, dTAF250, ire1, Multicatalytic Endopeptidase, Multicatalytic, mature T cell, Macroxyproteinase, 3000003C15Rik, TAF, constitutitional genetic, TREB-5, T Lymphocytes, Lymphocyte, Tax-responsive element-binding protein 5 homolog, Cancer, TAF[[II]]250, Malignant Neoplasm, Microscopies, Cryo electron Microscopy, Unfolded Protein Responses, body, l(3)84Ab, whole body, BG:DS00004.13, defective, Cistrons, Cell, Proteasome, dTAF230, Mus, p230, Protein, Neoplasm, TAF[[II]]250/230, TFIID, T lymphocyte, Lymphoid Cells, dire-1, opsonin activity, Taf[[II]]250, TAF[[II]]230, Prosome, Electron Cryomicroscopies, Bursa-Equivalent Lymphocyte, Lymphocytes, House Mice, 20S, TAF[II]250, IRE-like, Cancers, Laboratory Mice, DmelCG17603, DEL, B-lymphocyte proliferation, B cell receptor activity, Response, Variants, CG4583, Cryo-electron Microscopies, B-lymphocyte, multicatalytic endopeptidase, hereditary, Laboratory Mouse, General activity, Neoplasia, proteasome endopeptidase complex, Protein Responses, TAF1B Cells, Proteinase, Endopeptidase Complex, Malignant Neoplasm, postnatal development., Activity, B Lymphocytes, Bursa-Dependent Lymphocytes, Neoplasms, B cell, Benign Neoplasm, growth and development, Tumor, Malignant, Proteasome, development, Ingensin, Multicatalytic Proteinase, MT, Benign, Multicatalytic Endopeptidase Complex, Neoplasm, proteasome, B-cell, primary cancer, Malignancy, growth pattern, Macropain, Prosome, non-developmental growth, Complex, postnatal growth, Benign Neoplasms, 20S, Bursa-Equivalent Lymphocyte, Cancers, Proteasome Endopeptidase, 20S Proteasome, malignant tumor, Malignant Neoplasms, Neoplasias, Multicatalytic Endopeptidase, B lymphocyte, B-Lymphocyte, malignant neoplasm, Multicatalytic, Macroxyproteinase, 26S proteasome, Malignancies, B-lymphocyte, multicatalytic endopeptidase, growth, General activity, Neoplasia, proteasome endopeptidase complex, Cancer, TumorsPXD046953falseMidnolin stimulates proteasome activity necessary for lymphopoiesis and B cell cancer growthWe 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.Tue Nov 14 06:56:00 GMT 2023MSV000093397