PXD052471
PXD052471 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | SLFN11 Induces Apoptosis Through Ribosome Biogenesis Impairment |
Description | Impairment of ribosome biogenesis (RiBi) is triggered by the inhibition of rRNA synthesis and processing and leads to various biological effects. We discovered that Schlafen 11 (SLFN11)-dependent sensitization to replication stress produced by chemotherapeutic drugs induces RiBi impairment. Mechanistically, SLFN11 alters the chromatin structure of rDNA in response to replication stress, sequestering RNA polymerase I on chromatin while inhibiting rRNA synthesis and nucleolar R-loop formation. SLFN11-induced RiBi impairment inhibits translation overall, depleting extremely short-lived proteins, particularly MCL1, an ubiquitous anti-apoptotic protein. Consequently, SLFN11 activates apoptosis in an MCL1-dependent but TP53-independent manner. Comparable effects were observed with RNA polymerase I inhibitors and other RiBi inhibitory conditions regardless of SLFN11. These findings were validated across 34 diverse human cancer cell lines. Thus, we demonstrate that RiBi impairment is a robust inactivator of MCL1 and an activator of apoptosis and identify an additional mechanism by which SLFN11 sensitizes cancer cells to chemotherapeutic agents. |
HostingRepository | jPOST |
AnnounceDate | 2025-05-22 |
AnnouncementXML | Submission_2025-05-21_08:00:04.365.xml |
DigitalObjectIdentifier | |
ReviewLevel | Non peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Masaru Mori |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | S-carboxamidomethyl-L-cysteine; Acetyl; L-methionine sulfoxide |
Instrument | timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-05-22 01:59:53 | ID requested | |
⏵ 1 | 2025-05-21 08:00:04 | announced |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: SLFN11, apoptosis, ribosome biogenesis |
Contact List
Junko Murai | |
---|---|
lab head | |
Masaru Mori | |
contact affiliation | Nogoya University |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
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.jpostdb.org/JPST003116/ |