PXD050552-2

PXD050552 is an original dataset announced via ProteomeXchange.

Title	The ubiquitin E3 ligase APC/CCdc20 mediates mitotic degradation of OGT
Description	O-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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:06.883.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ke Qin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-12 00:40:48	ID requested
1	2024-08-10 12:04:09	announced
⏵ 2	2024-10-22 06:54:11	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: uterine carcinoma, ubiquitination, cell cycle,OGT, APC/CCdc20

Jing Li
contact affiliation	Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing 100048, China
contact email	jing_li@mail.cnu.edu.cn
lab head
Ke Qin
contact affiliation	Peking University
contact email	qinke@pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050552
     1. Label: PRIDE project
     2. Name: The ubiquitin E3 ligase APC/CCdc20 mediates mitotic degradation of OGT