PXD041851

PXD041851 is an original dataset announced via ProteomeXchange.

Title	Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage Response
Description	The DNA damage response (DDR) acts as a barrier to malignant transformation and is often impaired during tumorigenesis. Exploiting the impaired DDR can be a promising therapeutic strategy; however, the mechanisms of inactivation and corresponding biomarkers are incompletely understood. Starting from an unbiased screening approach, we identified the SMC5-SMC6 Complex Localization Factor 2 (SLF2) as a regulator of the DDR and biomarker for a B-cell lymphoma (BCL) patient subgroup with an adverse prognosis. SLF2-deficiency leads to loss of DDR factors including CLSPN and consequently impairs CHK1 activation. In line with this mechanism, genetic deletion of Slf2 drives lymphomagenesis in vivo. Tumor cells lacking SLF2 are characterized by a high level of DNA damage, which leads to alterations of the post-translational SUMOylation pathway as a safeguard. The resulting co-dependency confers synthetic lethality to a clinically applicable SUMOylation inhibitor (SUMOi), and inhibitors of the DDR pathway act highly synergistic with SUMOi. Together, our results identify SLF2 as a DDR regulator and reveal co-targeting of the DDR and SUMOylation as a promising strategy for the treatment of aggressive lymphoma.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:47.278.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan Müller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-27 08:22:14	ID requested
1	2023-07-21 09:09:21	announced
⏵ 2	2023-11-14 09:03:47	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: B-cell lymphoma,SLF2, Chromatin Proteome, DNA damage Response

Stefan Müller
contact affiliation	Institute of Biochemistry II, Goethe University Frankfurt, Medical School, 60590 Frankfurt, Germany
contact email	ste.mueller@em.uni-frankfurt.de
lab head
Stefan Müller
contact affiliation	Institute of Biochemistry II University Hospital Building 75 Theodor-Stern-Kai 7 60590 Frankfurt (Main)
contact email	ag-mueller@gmx.de
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/2023/07/PXD041851

PRIDE project URI

• PRIDE
  1. PXD041851
     1. Label: PRIDE project
     2. Name: Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage Response