Cell cycle phosphorylation dynamics in vivo reveals switch-like control of intrinsic disorder

ABSTRACT: 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.

ORGANISM(S): Xenopus Laevis

SUBMITTER: Juan Manuel Valverde  

PROVIDER: PXD026088 | panorama | Fri Oct 13 00:00:00 BST 2023

REPOSITORIES: PanoramaPublic