PXD041851 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-07-21 |
AnnouncementXML | Submission_2023-07-21_09:09:21.487.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | StefanMüller |
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 |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: B-cell lymphoma,SLF2, Chromatin Proteome, DNA damage Response |
Contact List
StefanMüller |
contact affiliation | Institute of Biochemistry II, Goethe University Frankfurt, Medical School, 60590 Frankfurt, Germany |
contact email | ste.mueller@em.uni-frankfurt.de |
lab head | |
StefanMüller |
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041851
- Label: PRIDE project
- Name: Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage Response