PXD026088

PXD026088 is an original dataset announced via ProteomeXchange.

Title	Cell cycle phosphorylation dynamics in vivo reveals switch-like control of intrinsic disorder
Description	Switch-like cyclin-dependent kinase (CDK)-1 activation is thought to underlie the abruptness of mitotic onset, but how CDKs can simultaneously phosphorylate many diverse substrates is unknown, and direct evidence for such phosphorylation dynamics in vivo is lacking. Here, we analysed protein phosphorylation states in single Xenopus embryos throughout synchronous cell cycles. 22% of 4583 phosphosites on 1843 proteins were dynamic in vivo. We assigned cell cycle phases using egg extracts, showing 693 S-phase and 1035 mitotic phosphorylations. High-time resolution targeted phosphoproteomics in single embryos revealed switch-like mitotic phosphorylation of diverse protein complexes. 60% of cell cycle-regulated phosphosites occurred in CDK consensus motifs, and 72% located to intrinsically disordered regions (IDRs). Dynamically phosphorylated proteins, and documented CDK substrates in human and yeast, are significantly more disordered than targets of other cell cycle kinases and phosphoproteins in general. Furthermore, 30-50% are components of membraneless organelles. Our results suggest that CDK-mediated phosphorylation of intrinsic disorder allows switch-like mitotic cellular reorganisation.
HostingRepository	PanoramaPublic
AnnounceDate	2023-10-13
AnnouncementXML	Submission_2023-10-13_10:39:58.179.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Juan Manuel Valverde
SpeciesList	scientific name: Xenopus laevis; NCBI TaxID: 8355;
ModificationList	Acetyl; Phospho; Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-19 06:19:38	ID requested
1	2023-10-12 10:12:02	announced
⏵ 2	2023-10-13 10:39:59	announced	: Added PubMed Id

Valverde JM, Dubra G, Phillips M, Haider A, Elena-Real C, Fournet A, Alghoul E, Chahar D, Andr, é, s-Sanchez N, Paloni M, Bernad, ó P, van Mierlo G, Vermeulen M, van den Toorn H, Heck AJR, Constantinou A, Barducci A, Ghosh K, Sibille N, Knipscheer P, Krasinska L, Fisher D, Altelaar M, A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation. Nat Commun, 14(1):6316(2023) [pubmed]

submitter keyword: phosphoproteomics, PRM, cell cycle, single cell

Maarten Altelaar
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, 3584 CH Utrecht, Netherlands
contact email	m.altelaar@uu.nl
lab head
Juan Manuel Valverde
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, 3584 CH Utrecht, Netherlands
contact email	j.m.valverdebarrantes@uu.nl
dataset submitter

Panorama Public dataset URI