PXD056448

PXD056448 is an original dataset announced via ProteomeXchange.

Title	Comparative ASCL1 interactome analysis reveals CDK2-Cyclin A2 as suppressors of differentiation in MYCN-amplified neuroblastoma
Description	Neuroblastoma is a heterogeneous paediatric cancer arising from developmentally arrested neuronal precursors, where restoring differentiation offers therapeutic promise. ASCL1, a pro-neural transcription factor, is widely expressed in neuroblastoma and can drive either proliferation or differentiation depending on the cellular context. Here, we show that distinct MYCN-amplified neuroblastoma cell lines exhibit differing cell cycle and differentiation responses to ASCL1 overexpression. By comparing genome-wide ASCL1 chromatin binding, transcriptional changes, and protein-protein interactions, we found that ASCL1 binds more extensively to neuronal proteins in a cell line that is more susceptible to ASCL1-driven differentiation, but associates with cell cycle regulators in less responsive cells. We show that CDK2-Cyclin A2 bind ASCL1 in less responsive cells, with CDK-mediated phosphorylation of ASCL1 limiting the ability of ASCL1 to drive differentiation. Our study reveals that context-dependent interactions of ASCL1 with protein partners on the chromatin control its ability to re-engage a differentiation program in neuroblastoma.
HostingRepository	PRIDE
AnnounceDate	2026-04-07
AnnouncementXML	Submission_2026-04-07_13:08:02.547.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valar Nila Roamio Franklin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-02 05:52:21	ID requested
⏵ 1	2026-04-07 13:08:03	announced

Dataset with its publication pending

submitter keyword: ASCL1, neuronal differentiation, MYCN-amplification, phosphorylation, CDK2,: Neuroblastoma, protein-protein interactions, interactome, Cyclin A2

Anna Philpott
contact affiliation	Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK
contact email	ap113@cam.ac.uk
lab head
Valar Nila Roamio Franklin
contact affiliation	Principal Scientific Associate
contact email	valar.franklin@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056448
     1. Label: PRIDE project
     2. Name: Comparative ASCL1 interactome analysis reveals CDK2-Cyclin A2 as suppressors of differentiation in MYCN-amplified neuroblastoma