PXD012954

PXD012954 is an original dataset announced via ProteomeXchange.

Title	Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:29:08.129.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Enrico Massignani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; phenyl isocyanate derivatized residue; N6-propanoyl-L-lysine; acetylated residue; dimethylated residue; N6,N6,N6-trimethyl-L-lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 01:48:46	ID requested
⏵ 1	2024-10-07 13:29:08	announced

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]

ProteomeXchange project tag: EPIC-XS, biomedical

submitter keyword: LSD1 inhibitors, LSD1,Acute Myeloid Leukemia, protein-protein interaction

Tiziana Bonaldi
contact affiliation	Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
contact email	tiziana.bonaldi@ieo.it
lab head
Enrico Massignani
contact affiliation	European Institute of Oncology IRCSS, Department of Experimental Oncology, Milan, Italy
contact email	enrico.massignani@ieo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/05/PXD012954

PRIDE project URI

• PRIDE
  1. PXD012954
     1. Label: PRIDE project
     2. Name: Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation