PXD048838

PXD048838 is an original dataset announced via ProteomeXchange.

Title	Positively charged specificity site in cyclin B1 is essential for mitotic fidelity
Description	Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force of cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity is still poorly understood. Here, we discovered that a positively charged pocket in cyclin B1, which is exclusively conserved within B-type cyclins and binds phosphorylated serine- or threonine-residues as well as acidic side chains, is essential for correct execution of mitosis. HeLa cells expressing pocket mutant cyclin B1 are strongly delayed in anaphase onset due to multiple defects in mitotic spindle function and timely activation of the E3-ligase APC/C. Non-functional pocket results in decreased APC/C phosphorylation at non-consensus CDK1 sites, compromised in vitro ubiquitylation activity, and reduced binding of the E2-enzyme UBE2S. Our results support a model in which cyclin B1’s pocket serves as specificity factor for sequential substrate phosphorylations involving initial priming events facilitating subsequent pocket-dependent phosphorylations at non-consensus CDK1 motifs.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:41:54.736.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-24 07:33:58	ID requested
⏵ 1	2025-05-06 12:41:55	announced

10.1038/s41467-024-55669-x;

submitter keyword: cyclin B, phosphate-binding pocket, mitosis, spindle,CDK1, APC/C, Ube2S

Prof Dr Florian Stengel
contact affiliation	Laboratory of Biochemistry and Mass Spectrometry, Department of Biology, University of Konstanz
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048838
     1. Label: PRIDE project
     2. Name: Positively charged specificity site in cyclin B1 is essential for mitotic fidelity