PXD018365

PXD018365 is an original dataset announced via ProteomeXchange.

Title	The USP7-TRIM27 axis as part of non-canonical PRC1.1 is a druggable target in leukemia
Description	In an attempt to unravel the functionality and targettability of the non-canonical PRC1.1 Polycomb complex in human leukemogenesis, we dissected the subunit composition of the PRC1.1 complex and show that USP7 and TRIM27 are integral components. USP7 interactome analyses show that PRC1.1 is the predominant Polycomb complex co-precipitating with USP7. USP7 inhibition results in PRC1.1 disassembly and loss of chromatin binding, coinciding with reduced H2AK119ub and H3K27ac levels and diminished gene transcription of active PRC1.1-controlled loci, whereas H3K4me3 levels remain unaffected. TRIM27 and USP7 are reciprocally required for incorporation into PRC1.1, and TRIM27 knockdown partially rescues USP7 inhibitor sensitivity. USP7 inhibitors effectively impair proliferation in (primary) AML cells in vitro, also independent of the USP7-MDM2-TP53 axis, and MLL-AF9-induced leukemia is significantly delayed in vivo in human leukemia xenografts. We propose a model where USP7 counteracts TRIM27 E3 ligase activity, thereby maintaining PRC1.1 integrity and function. Moreover, USP7 inhibition may be a promising new strategy to treat AML patients.
HostingRepository	PRIDE
AnnounceDate	2021-06-14
AnnouncementXML	Submission_2021-06-14_03:35:43.394.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent van den Boom
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-04 09:25:39	ID requested
⏵ 1	2021-06-14 03:35:44	announced

Maat H, Atsma TJ, Hogeling SM, Rodr, í, guez L, ó, pez A, Jaques J, Olthuis M, de Vries MP, Gravesteijn C, Brouwers-Vos AZ, van der Meer N, Datema S, Salzbrunn J, Huls G, Baas R, Martens JHA, van den Boom V, Schuringa JJ, The USP7-TRIM27 axis mediates non-canonical PRC1.1 function and is a druggable target in leukemia. iScience, 24(5):102435(2021) [pubmed]

submitter keyword: Leukemia, Polycomb, PRC1.1, USP7, TRIM27

Jan Jacob Schuringa
contact affiliation	1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
contact email	j.j.schuringa@umcg.nl
lab head
Vincent van den Boom
contact affiliation	Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen.
contact email	v.van.den.boom@umcg.nl
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/2021/06/PXD018365

PRIDE project URI

• PRIDE
  1. PXD018365
     1. Label: PRIDE project
     2. Name: The USP7-TRIM27 axis as part of non-canonical PRC1.1 is a druggable target in leukemia