Publikation:

Positively charged specificity site in cyclin B1 is essential for mitotic fidelity

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2025

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Höfler, Anna
Yu, Jun
Kremer, Nora
Schunk, Rebecca
Bange, Tanja
Boland, Andreas

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http://nbn-resolving.de/urn:nbn:de:bsz:352-2-12zhxt0g6btry4
DOI (zitierfähiger Link)
https://doi.org/10.1038/s41467-024-55669-x
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CC BY 4.0

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Deutsche Forschungsgemeinschaft (DFG): 5041140321
Deutsche Forschungsgemeinschaft (DFG): INST 86/1800-1 FUGG
Deutsche Forschungsgemeinschaft (DFG): 532411725
Deutsche Forschungsgemeinschaft (DFG): SFB969/B01
Deutsche Forschungsgemeinschaft (DFG): 496470458
Swiss National Science Foundation: TMSGI3_211581

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Biologie: Publikationen
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Published

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Nature Communications. Springer. 2025, 16(1), 853. eISSN 2041-1723. Verfügbar unter: doi: 10.1038/s41467-024-55669-x

Zusammenfassung

Phosphorylation of substrates by cyclin-dependent kinases (CDKs) is the driving force of cell cycle progression. Several CDK-activating cyclins are involved, yet how they contribute to substrate specificity is still poorly understood. Here, we discover that a positively charged pocket in cyclin B1, which is exclusively conserved within B-type cyclins and binds phosphorylated serine- or threonine-residues, is essential for correct execution of mitosis. HeLa cells expressing pocket mutant cyclin B1 are strongly delayed in anaphase onset due to multiple defects in mitotic spindle function and timely activation of the E3 ligase APC/C. Pocket integrity is essential for APC/C phosphorylation particularly at non-consensus CDK1 sites and full in vitro ubiquitylation activity. Our results support a model in which cyclin B1’s pocket facilitates sequential substrate phosphorylations involving initial priming events that assist subsequent pocket-dependent phosphorylations even at non-consensus CDK1 motifs.

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570 Biowissenschaften, Biologie

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ISO 690HEINZLE, Christian, Anna HÖFLER, Jun YU, Peter HEID, Nora KREMER, Rebecca SCHUNK, Florian STENGEL, Tanja BANGE, Andreas BOLAND, Thomas U. MAYER, 2025. Positively charged specificity site in cyclin B1 is essential for mitotic fidelity. In: Nature Communications. Springer. 2025, 16(1), 853. eISSN 2041-1723. Verfügbar unter: doi: 10.1038/s41467-024-55669-x
BibTex
@article{Heinzle2025-01-20Posit-72271,
  title={Positively charged specificity site in cyclin B1 is essential for mitotic fidelity},
  year={2025},
  doi={10.1038/s41467-024-55669-x},
  number={1},
  volume={16},
  journal={Nature Communications},
  author={Heinzle, Christian and Höfler, Anna and Yu, Jun and Heid, Peter and Kremer, Nora and Schunk, Rebecca and Stengel, Florian and Bange, Tanja and Boland, Andreas and Mayer, Thomas U.},
  note={Article Number: 853}
}
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