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PXD052471

PXD052471 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSLFN11 Induces Apoptosis Through Ribosome Biogenesis Impairment
DescriptionImpairment 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.
HostingRepositoryjPOST
AnnounceDate2025-05-22
AnnouncementXMLSubmission_2025-05-21_08:00:04.365.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMasaru Mori
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListS-carboxamidomethyl-L-cysteine; Acetyl; L-methionine sulfoxide
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-22 01:59:53ID requested
12025-05-21 08:00:04announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SLFN11, apoptosis, ribosome biogenesis
Contact List
Junko Murai
lab head
Masaru Mori
contact affiliationNogoya University
dataset submitter
Full Dataset Link List
jPOST dataset URI
Dataset FTP location
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