PXD039332-2

PXD039332 is an original dataset announced via ProteomeXchange.

Title	The Super Elongation Complex Drives Transcriptional Addiction in MYCN-amplified Neuroblastoma
Description	MYCN amplification in neuroblastoma leads to aberrant expression of MYCN oncoprotein, which binds active genes promoting transcriptional amplification. Yet how MYCN coordinates transcription elongation to meet productive transcriptional amplification and which elongation machinery represents MYCN-driven vulnerability remain to be identified. We conducted a targeted screen of transcription elongation factors and identified the super elongation complex (SEC) as a unique vulnerability in MYCN-amplified neuroblastomas. MYCN directly binds EAF1 and recruits SEC to enhance processive transcription elongation. Depletion of EAF1 or AFF1/AFF4, another core subunit of SEC, leads to a global reduction in transcription elongation and elicits selective apoptosis of MYCN-amplified neuroblastoma cells. A combination screen reveals SEC inhibition synergistically potentiates the therapeutic efficacies of FDA-approved BCL2 antagonist ABT-199, in part due to suppression of MCL1 expression, both in MYCN-amplified neuroblastoma cells and in patient-derived xenografts. These findings identify disruption of the MYCN-SEC regulatory axis as a promising therapeutic strategy in neuroblastoma.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:04.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donghai Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-09 02:31:46	ID requested
1	2023-05-10 13:53:56	announced
⏵ 2	2023-11-14 08:47:05	announced	2023-11-14: Updated project metadata.

Wang D, Yin Z, Wang H, Wang L, Li T, Xiao R, Xie T, Han R, Dong R, Liu H, Liang K, Qing G, -amplified neuroblastoma. Sci Adv, 9(13):eadf0005(2023) [pubmed]

submitter keyword: MYCN, Neuroblastoma,Super elongation complex (SEC), Transcription elongation, ABT-199

Hudan Liu
contact affiliation	Medical Research Institute, Wuhan University
contact email	hudanliu@whu.edu.cn
lab head
Donghai Wang
contact affiliation	Wuhan University Medical Research Institute
contact email	wdhseer@whu.edu.cn
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/2023/05/PXD039332

PRIDE project URI

• PRIDE
  1. PXD039332
     1. Label: PRIDE project
     2. Name: The Super Elongation Complex Drives Transcriptional Addiction in MYCN-amplified Neuroblastoma