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PXD012954

PXD012954 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation
DescriptionThe histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells through degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knock-out, but LSD1 inhibition sensitizes them to physiological doses of RA without altering the stability of PML-RAR, and extends survival of leukemic mice upon RA treatment. Non-enzymatic activities of LSD1 are essential to block differentiation of leukemic cells, while the combination of LSD1 inhibitors (or LSD1 knock-out) with low doses of RA releases a differentiation-associated gene expression program, not strictly dependent on changes in histone H3K4 methylation (known substrate of LSD1). An integrated proteomic/epigenomic/mutational analysis showed that LSD1 inhibitors alter the recruitment of LSD1-containing complexes to chromatin through inhibition of the interaction between LSD1 and GFI1, a relevant transcription factor in hematopoiesis.
HostingRepositoryPRIDE
AnnounceDate2024-10-07
AnnouncementXMLSubmission_2024-10-07_13:29:08.129.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEnrico Massignani
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonomethylated residue; phenyl isocyanate derivatized residue; N6-propanoyl-L-lysine; acetylated residue; dimethylated residue; N6,N6,N6-trimethyl-L-lysine
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-05 01:48:46ID requested
12024-10-07 13:29:08announced
Publication List
10.1126/sciadv.aax2746;
Ravasio R, Ceccacci E, Nicosia L, Hosseini A, Rossi PL, Barozzi I, Fornasari L, Zuffo RD, Valente S, Fioravanti R, Mercurio C, Varasi M, Mattevi A, Mai A, Pavesi G, Bonaldi T, Minucci S, Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for retinoic acid-induced differentiation. Sci Adv, 6(15):eaax2746(2020) [pubmed]
Keyword List
ProteomeXchange project tag: EPIC-XS, biomedical
submitter keyword: LSD1 inhibitors, LSD1,Acute Myeloid Leukemia, protein-protein interaction
Contact List
Tiziana Bonaldi
contact affiliationDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
contact emailtiziana.bonaldi@ieo.it
lab head
Enrico Massignani
contact affiliationEuropean Institute of Oncology IRCSS, Department of Experimental Oncology, Milan, Italy
contact emailenrico.massignani@ieo.it
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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