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PXD012305

PXD012305 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes
DescriptionNucleophosmin (NPM1) is either frequently mutated or subjected to chromosomal translocation in acute myeloid leukemia (AML). NPM protein is primarily located in the nucleus, but the recurrent NPMc+ mutation is characterized by cytoplasmic localization and leukemogenic properties. Similarly, the NPM-MLF1 translocation product favors the partial cytoplasmic retention of NPM. Regardless of their common cellular distribution, NPM-MLF1 malignancies engender different effects on hematopoiesis compared to NPMc+ counterparts, highlighting possible aberrant nuclear function(s) of NPM in NPMc+ and NPM-MLF1 AML. We performed a proteomics analysis and found that NPM and NPM-MLF1 interact with chromatin remodeling complexes of the ISWI family, as well as with NuRD and P/BAF complexes. Accordingly, NPM and NPM-MLF1 are recruited to transcriptionally active or repressed genes along with NuRD and P/BAF elements. Although the overall gene expression program in NPM knockdown cells is similar to that resulting from NPMc+ and is consistent with loss of nuclear function of NPM, NPM-MLF1 expression differentially altered gene transcription regulated by NPM. The abnormal gene regulation imposed by NPM-MLF1 is characterized by enhanced recruitment of NuRD to gene regulatory regions. Thus, different mechanisms orchestrate the deregulation of NPM function in NPMc+ -versus NPM1-MLF1- associated leukemia.
HostingRepositoryPRIDE
AnnounceDate2019-10-18
AnnouncementXMLSubmission_2019-11-12_02:10:43.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Milot
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-11 04:51:30ID requested
12019-10-17 23:39:11announced
22019-11-12 02:10:44announced2019-11-12: Updated publication reference for PubMed record(s): 31675375.
Publication List
Darracq A, Pak H, Bourgoin V, Zmiri F, Dellaire G, Affar EB, Milot E, NPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes. PLoS Genet, 15(11):e1008463(2019) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: NPM, NPM-MLF1, leukemia, chromatin remodeling complexes, proteomic, epigenetic
Contact List
Dr Milot Eric
contact affiliation(1) Maisonneuve Rosemont Hospital Research Center, CIUSSS Est de l’Île de Montréal, Montreal, QC, Canada (2) Department of Medicine, University of Montreal, Montréal, QC, Canada
contact emaile.milot.1@umontreal.ca
lab head
Eric Milot
contact affiliationUniversité de Montréal
contact emailemilot.hmr@ssss.gouv.qc.ca
dataset submitter
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Dataset FTP location
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PRIDE project URI
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