PXD012172-2

PXD012172 is an original dataset announced via ProteomeXchange.

Title	Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma
Description	Resistance 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.
HostingRepository	PRIDE
AnnounceDate	2020-02-21
AnnouncementXML	Submission_2020-05-18_06:50:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hector Huang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-24 01:36:19	ID requested
1	2020-02-21 01:00:19	announced
⏵ 2	2020-05-18 06:50:55	announced	2020-05-18: Updated publication reference for PubMed record(s): 32321912.
3	2024-10-22 04:51:27	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biomedical

submitter keyword: multiple myeloma, cancer, LC-MSMS phosphoproteomics, proteasome inhibition, splicing, alternative splicing, spliceosome, splice factor

Arun Paul Wiita
contact affiliation	Department of Laboratory Medicine and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, United States of America
contact email	arun.wiita@ucsf.edu
lab head
Hector Huang
contact affiliation	UCSF
contact email	hector.huang@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/02/PXD012172

PRIDE project URI

• PRIDE
  1. PXD012172
     1. Label: PRIDE project
     2. Name: Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma