PXD061458

PXD061458 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	CRL3-GMCL1 mediates 53BP1 degradation, promoting evasion from mitotic surveillance upon paclitaxel treatment
Description	The Mitotic Surveillance Pathway (MSP) is a critical quality control mechanism that monitors mitosis duration. Prolonged mitosis - caused by genomic defects, spindle errors, or anti-mitotic drugs such as paclitaxel - induces formation of the ternary -mitotic stopwatch- complex composed of 53BP1, USP28, and p53. This complex protects p53 from MDM2-mediated degradation, and its accumulation transmits a memory of the delayed mitosis to the daughter cells, where p53 signaling triggers cell cycle arrest and apoptosis. In Paclitaxel-resistant cancers, cells bypass the MSP, enabling unchecked proliferation and survival, though the underlying mechanisms remain unknown. Here, we identify CRL3GMCL1 as the ubiquitin ligase that targets 53BP1 for degradation during prolonged M phase. In cancers with high GMCL1 levels, the CRL3GMCL1-mediated degradation of 53BP1 prevents the formation of the mitotic stopwatch complex, leading to p53 degradation and sustained proliferation. Loss of GMCL1 stabilizes mitotic 53BP1 levels and restores paclitaxel sensitivity. Our results indicate that combining GMCL1 inhibition with taxane treatment represent a novel strategy to restore taxane sensitivity in cancers. The mass spectrometric data files for the protein complex analysis of FLAG-tagged: (i) wild-type GMCL1 (GMCL1 WT), (ii) a GMCL1 E142K mutant (GMCL1 EK for short), which disrupts its ability to bind with CUL3, and (iii) a GMCL1 BTB/BACK-only mutant, which misses GMCL1's putative C-terminal substrate-binding domain are included in this entry.
HostingRepository	MassIVE
AnnounceDate	2026-01-16
AnnouncementXML	Submission_2026-01-16_08:12:50.623.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Beatrix Ueberheide
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation
Instrument	Orbitrap Eclipse

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-04 07:57:25	ID requested
⏵ 1	2026-01-16 08:12:51	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: Mitotic Surveillance Pathway, Germ cell-less protein-like 1, TP53-binding protein 1, paclitaxel treatment, DatasetType:Proteomics

submitter keyword: Mitotic Surveillance Pathway, Germ cell-less protein-like 1, TP53-binding protein 1, paclitaxel treatment, DatasetType:Proteomics

Contact List

Beatrix M Ueberheide
contact affiliation	NYU Langone Grossman School of Medicine
contact email	beatrix.ueberheide@nyulangone.org
lab head
Beatrix Ueberheide
contact affiliation	NYU School of Medicine
contact email	beatrixueberheide@gmail.com
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE 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://massive-ftp.ucsd.edu/v09/MSV000097235/