CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock

Francesca Carrieri, Philip Murray, Dimitrinka Ditsova, Margaret Ashley Ferris, Paul Davies, Kim Dale (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
275 Downloads (Pure)


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.
Original languageEnglish
Article numbere46436
Pages (from-to)1-22
Number of pages22
JournalEMBO Reports
Issue number7
Early online date17 Apr 2019
Publication statusPublished - 1 Jul 2019


  • FBXW7
  • Notch
  • cell cycle
  • phosphorylation
  • somitogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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