PXD013038

PXD013038 is an original dataset announced via ProteomeXchange.

Title	CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock
Description	All vertebrates share a segmented body axis. Segments form from the rostral end of the presomitic mesoderm (PSM) with a periodicity that is regulated by the segmentation clock. The segmentation clock is a molecular oscillator that exhibits dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanism by which NICD stability is regulated in this context is unclear. We identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations and an increase in somite size.
HostingRepository	PRIDE
AnnounceDate	2019-04-23
AnnouncementXML	Submission_2019-04-23_05:30:52.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013038
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	francesca anna carrieri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Phospho; Oxidation; Dioxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-11 03:50:27	ID requested
⏵ 1	2019-04-23 05:30:54	announced

submitter keyword: Cell cycle, FBXW7, Notch, Phosphorylation, Signalling, Somitogenesis

Jacqueline Kim Dale
contact affiliation	Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD15EH, Scotland, UK.
contact email	j.k.dale@dundee.ac.uk
lab head
francesca anna carrieri
contact affiliation	University of Dundee
contact email	facarrieri@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013038
     1. Label: PRIDE project
     2. Name: CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock