ArticleEMBO reports2019
CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 64 citations in OpenAlex.
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids.Genes & development · 2025Article
- Speed of life: tuning the ticktock of the segmentation clock.Genes & development · 2025Article
- Cellular and molecular control of vertebrate somitogenesis.Nature reviews. Molecular cell biology · 2024Review
- Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.International journal of molecular sciences · 2024Review
- FBP1 inhibits NSCLC stemness by promoting ubiquitination of Notch1 intracellular domain and accelerating degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Uncovering NOTCH1 as a Promising Target in the Treatment ofInternational journal of molecular sciences · 2023Article
- The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer.Cancers · 2023Article
- Hydroxylation of the NOTCH1 intracellular domain regulates Notch signaling dynamics.Cell death & disease · 2022Article
- ATR activity controls stem cell quiescence via the cyclin F-SCF complex.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Notch controls the cell cycle to define leader versus follower identities during collective cell migration.eLife · 2022Article
- Signalling dynamics in embryonic development.The Biochemical journal · 2021Review
- Notch signaling in reproduction.Trends in endocrinology and metabolism: TEM · 2021Review
- Supervised learning based on tumor imaging and biopsy transcriptomics predicts response of hepatocellular carcinoma to transarterial chemoembolization.Cell reports. Medicine · 2021Article
- Differential phase register of Hes1 oscillations with mitoses underlies cell-cycle heterogeneity in ERProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.Nature communications · 2020Article
- Decoding the PTM-switchboard of Notch.Biochimica et biophysica acta. Molecular cell research · 2019Review
- A tale of two clocks: phosphorylation of NICD by CDKs links cell cycle and segmentation clock.EMBO reports · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.