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PXD050552-1

PXD050552 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe ubiquitin E3 ligase APC/CCdc20 mediates mitotic degradation of OGT
DescriptionO-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is the sole enzyme that catalyzes all O-GlcNAcylation reactions intracellularly. Previous investigations have found that OGT levels oscillate during the cell division process. Specifically, OGT abundance is downregulated during mitosis, but the underlying mechanism is lacking. Here we demonstrate that OGT is ubiquitinated by the ubiquitin E3 ligase, anaphase promoting complex/cyclosome (APC/C)-cell division cycle 20 (Cdc20). We show that APC/CCdc20 interacts with OGT through a conserved destruction box (D-box): Arg-351/Leu-354, the abrogation of which stabilizes OGT. As APC/CCdc20-substrate binding is often preceded by a priming ubiquitination event, we also used mass spectrometry and mapped OGT Lys-352 to be a ubiquitination site, which is a prerequisite for OGT association with APC/C subunits. Interestingly in The Cancer Genome Atlas, R351C is a uterine carcinoma mutant, suggesting that mutations of the D-box are linked with tumorigenesis. Paradoxically, we found that both R351C and the D-box mutants (R351A/L354A) inhibit uterine carcinoma in mouse xenograft models, probably due to impaired cell division and proliferation. In sum, we propose a model where OGT Lys-352 ubiquitination primes its binding with APC/C, and then APC/CCdc20 partners with OGT through the D-box for its mitotic destruction. Our work not only highlights the key mechanism that regulates OGT during the cell cycle, but also reveals the mutual coordination between glycosylation and the cell division machinery.
HostingRepositoryPRIDE
AnnounceDate2024-08-10
AnnouncementXMLSubmission_2024-08-10_12:04:08.274.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKe Qin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitination signature dipeptidyl lysine
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-12 00:40:48ID requested
12024-08-10 12:04:09announced
22024-10-22 06:54:11announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.jbc.2024.107448;
Meng L, Dong R, Mi W, Qin K, Ouyang K, Sun J, Li J, mediates mitotic degradation of OGT. J Biol Chem, 300(7):107448(2024) [pubmed]
Keyword List
submitter keyword: uterine carcinoma, ubiquitination, cell cycle,OGT, APC/CCdc20
Contact List
Jing Li
contact affiliationBeijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing 100048, China
contact emailjing_li@mail.cnu.edu.cn
lab head
Ke Qin
contact affiliationPeking University
contact emailqinke@pku.edu.cn
dataset submitter
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Dataset FTP location
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