PXD022518

PXD022518 is an original dataset announced via ProteomeXchange.

Title	Nuclear Condensation of NUP98-Fusion Proteins drives leukemogenic gene expression NUP98-fusion protein drive oncogenic gene expression via nuclear/biomolecular condensation
Description	NUP98-fusion proteins cause leukemia via unknown molecular mechanisms. All NUP98-fusion proteins share an intrinsically disordered region (IDR) featuring >35 repeats of Phenylalanine-Glycine (FG) in the NUP98 N-terminus. Conversely, C-terminal NUP98-fusion partners often have critical functions in gene control. Given these structural features we hypothesized that mechanisms of oncogenic transformation by NUP98-fusion proteins are hard-wired in their protein interactomes. Affinity purification coupled to mass spectrometry and confocal imaging of five distinct NUP98-fusion proteins revealed that conserved interactors were enriched for proteins involved in biomolecular condensation and that they co-localized with NUP98-fusion proteins in nuclear puncta. We developed biotinylated isoxazole-mediated condensome mass spectrometry (biCon-MS) to show that NUP98-fusion proteins alter the global composition of biomolecular condensates. An artificial FG-repeat-containing fusion protein phenocopied the nuclear localization patterns of NUP98-fusion proteins and their capability to drive oncogenic gene expression programs. Thus, we propose that IDR-containing fusion proteins uniquely combine biomolecular condensation with transcriptional control to induce cancer.
HostingRepository	PRIDE
AnnounceDate	2020-12-23
AnnouncementXML	Submission_2020-12-23_11:22:15.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022518
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andre Mueller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-13 04:10:37	ID requested
⏵ 1	2020-12-23 11:22:15	announced

Dataset with its publication pending

submitter keyword: AML, NUP98, fusion protein, AP-MS, biCon-MS, condensate

Florian Grebien
contact affiliation	Institute for Medical Biochemistry, University of Veterinary Medicine, Vienna, 1210, Austria
contact email	florian.grebien@vetmeduni.ac.at
lab head
Andre Mueller
contact affiliation	Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	amueller@cemm.oeaw.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022518
     1. Label: PRIDE project
     2. Name: Nuclear Condensation of NUP98-Fusion Proteins drives leukemogenic gene expression NUP98-fusion protein drive oncogenic gene expression via nuclear/biomolecular condensation