PXD022164 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Indisulam targets RNA splicing and metabolism to serve as a novel therapeutic strategy for high-risk neuroblastoma |
Description | Neuroblastoma is the most common solid tumour in childhood and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be particularlysensitive to indisulam, a molecular glue that selectively targets the RNA splicing factor RBM39 for proteosomal degradation via DCAF15-E3-ubiquitin ligase. In neuroblastoma models indisulam induced rapid loss of RBM39, accumulation of splicing errors and growth inhibition in a DCAF15-dependent manner. Integrative analysis of RNAseq and proteomics data highlighted a particular disruption to cell cycle and metabolism. Metabolic profiling demonstrated metabolome perturbations and mitochondrial dysfunction resulting from indisulam. Complete tumour without relapse was observed in both xenografts and the Th-MYCN transgenic model of neuroblastoma after indisulam treatment, with RBM39 loss confirmed in vivo. Our data imply that dual targeting of metabolism and RNA splicing with anti-cancer sulfonamides such as indisulam is promising therapeutic approach for high-risk neuroblastoma. |
HostingRepository | PRIDE |
AnnounceDate | 2022-01-13 |
AnnouncementXML | Submission_2022-01-13_09:27:39.322.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alex Montoya |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-26 01:01:55 | ID requested | |
⏵ 1 | 2022-01-13 09:27:39 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, cancer cells, LC-MSMS, drug treatment |
Contact List
Dr Hector Keun |
contact affiliation | Imperial College London, Faculty of Medicine, Department of Surgery & Cancer |
contact email | h.keun@imperial.ac.uk |
lab head | |
Alex Montoya |
contact affiliation | Medical Research Council - London Institute of Medical Sciences |
contact email | alex.montoya@lms.mrc.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022164
- Label: PRIDE project
- Name: Indisulam targets RNA splicing and metabolism to serve as a novel therapeutic strategy for high-risk neuroblastoma