PXD009020 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Pathogenesis of dominant-negative mutant GFI1B and associated proteomic abnormalities in megakaryocytes and platelets |
Description | Dominant-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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:43:16.141.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johanna Koornneef |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetic acid derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-02-23 03:30:37 | ID requested | |
1 | 2019-01-25 06:01:50 | announced | |
⏵ 2 | 2024-10-22 04:43:24 | announced | 2024-10-22: 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 affiliation | Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands |
contact email | s.meijer@sanquin.nl |
lab head | |
Johanna Koornneef |
contact affiliation | Sanquin Research, Amsterdam, The Netherlands |
contact email | a.koornneef@sanquin.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009020
- Label: PRIDE project
- Name: Pathogenesis of dominant-negative mutant GFI1B and associated proteomic abnormalities in megakaryocytes and platelets