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PXD012172 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma
DescriptionResistance to proteasome inhibitors (PIs) is a ubiquitous clinical concern in multiple myeloma. We proposed that signaling-level responses after PI would reveal new means to enhance efficacy. Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on spliceosome components. Spliceosome modulation was invisible to RNA or protein abundance alone. Transcriptome analysis demonstrated broad-scale intron retention suggestive of PI-specific splicing interference. Direct spliceosome inhibition synergized with carfilzomib and showed potent anti-myeloma activity. Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHector Huang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-12-24 01:36:19ID requested
12020-02-21 01:00:19announced
22020-05-18 06:50:55announced2020-05-18: Updated publication reference for PubMed record(s): 32321912.
Publication List
Huang HH, Ferguson ID, Thornton AM, Bastola P, Lam C, Lin YT, Choudhry P, Mariano MC, Marcoulis MD, Teo CF, Malato J, Phojanakong PJ, Martin TG, Wolf JL, Wong SW, Shah N, Hann B, Brooks AN, Wiita AP, Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma. Nat Commun, 11(1):1931(2020) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: multiple myeloma, cancer, LC-MSMS phosphoproteomics, proteasome inhibition, splicing, alternative splicing, spliceosome, splice factor
Contact List
Arun Paul Wiita
contact affiliationDepartment of Laboratory Medicine and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, United States of America
contact emailarun.wiita@ucsf.edu
lab head
Hector Huang
contact affiliationUCSF
contact emailhector.huang@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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