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PXD009020

PXD009020 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePathogenesis of dominant-negative mutant GFI1B and associated proteomic abnormalities in megakaryocytes and platelets
DescriptionDominant-negative mutations in transcription factor Growth Factor Independence-1B (GFI1B) cause a bleeding disorder characterized by a plethora of megakaryocyte and platelet abnormalities. The deregulated molecular mechanisms and pathways are unknown. Here we show that normal and mutant GFI1B interacted most strongly with the LSD1-RCOR-HDAC corepressor complex in megakaryoblasts. Sequestration of this complex by mutant GFI1B and chemical separation of GFI1B from LSD1 induced abnormalities in normal megakaryocytes comparable to those seen in patients. Megakaryocytes derived from GFI1B-mutant induced pluripotent stem cells (iPSC) also phenocopied abnormalities seen in patients. Proteome studies on normal and mutant iPSC-derived megakaryocytes identified a multitude of deregulated pathways downstream of mutant GFI1B. Proteome studies on primary normal and GFI1B-mutant platelets showed reduced expression of proteins implicated in platelet function, and sustained expression of proteins normally downregulated during megakaryocyte differentiation. Thus, GFI1B regulates a broad developmental program during megakaryopoiesis. Mutant GFI1B deregulates this program through LSD1-RCOR-HDAC sequestering.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:43:16.141.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohanna Koornneef
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetic acid derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-02-23 03:30:37ID requested
12019-01-25 06:01:50announced
22024-10-22 04:43:24announced2024-10-22: Updated project metadata.
Publication List
10.3324/haematol.2018.194555;
van Oorschot R, Hansen M, Koornneef JM, Marneth AE, Bergevoet SM, van Bergen MGJM, van Alphen FPJ, van der Zwaan C, Martens JHA, Vermeulen M, Jansen PWTC, Baltissen MPA, Gorkom BAPL, Janssen H, Jansen JH, von Lindern M, Meijer AB, van den Akker E, van der Reijden BA, mutation and its affected pathways in megakaryocytes and platelets. Haematologica, 104(7):1460-1472(2019) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: megakaryocytes, LSD1, bleeding disorder, LC-MS,Proteomics, platelet, GFI1B
Contact List
Alexander Meijer
contact affiliationDepartment of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
contact emails.meijer@sanquin.nl
lab head
Johanna Koornneef
contact affiliationSanquin Research, Amsterdam, The Netherlands
contact emaila.koornneef@sanquin.nl
dataset submitter
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Dataset FTP location
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PRIDE project URI
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