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The cAMP-PKA signaling initiates mitosis by phosphorylating Bora

Author

Listed:
  • Min Zhu

    (Zhejiang University)

  • Shinan Zhou

    (Zhejiang University)

  • Yingqi Zhang

    (Zhejiang University)

  • Qinfu Chen

    (Zhejiang University)

  • Xueying Yuan

    (Zhejiang University)

  • Long Zhang

    (Zhejiang University)

  • Haiyan Yan

    (Hangzhou City University)

  • Fangwei Wang

    (Zhejiang University
    Zhejiang University
    State Key Laboratory of Transvascular Implantation Devices
    Zhejiang University)

Abstract

Timely entry into mitosis requires activation of Polo-like kinase 1 (Plk1) by Aurora kinase A (Aurora A), but the upstream signaling trigger remains unclear. Here, we show that cyclic AMP (cAMP) signaling serves as a critical initiator of mitosis in mammalian cells. Specifically, the cAMP-dependent protein kinase (PKA) phosphorylates Bora, enabling it to bind Aurora A and recruit it to the Bora-Plk1 complex during G2 phase, thereby facilitating Aurora A-dependent activation of Plk1. Disruption of PKA-mediated Bora phosphorylation or the Bora-Aurora A interaction impairs Plk1 activation and delays the G2-to-mitosis (G2/M) transition. Conversely, a phospho-mimetic Bora mutant bypasses the requirement for PKA in promoting Bora-Aurora A interaction, Plk1 activation, and mitotic entry. Furthermore, PKA-mediated Bora phosphorylation and the resulting Bora-Aurora A interaction are essential for mitotic entry during DNA damage checkpoint recovery. Together, these findings identify the cAMP-PKA-Bora-Aurora A-Plk1 signaling cascade as a previously unrecognized and critical trigger for mitotic commitment.

Suggested Citation

  • Min Zhu & Shinan Zhou & Yingqi Zhang & Qinfu Chen & Xueying Yuan & Long Zhang & Haiyan Yan & Fangwei Wang, 2025. "The cAMP-PKA signaling initiates mitosis by phosphorylating Bora," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63352-y
    DOI: 10.1038/s41467-025-63352-y
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    References listed on IDEAS

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    1. Grégory Eot-Houllier & Laura Magnaghi-Jaulin & Géraldine Fulcrand & François-Xavier Moyroud & Solange Monier & Christian Jaulin, 2018. "Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    2. Fumiko Toyoshima-Morimoto & Eri Taniguchi & Nobuko Shinya & Akihiro Iwamatsu & Eisuke Nishida, 2001. "Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase," Nature, Nature, vol. 410(6825), pages 215-220, March.
    3. N. Tavernier & Y. Thomas & S. Vigneron & P. Maisonneuve & S. Orlicky & P. Mader & S. G. Regmi & L. Hove & N. M. Levinson & G. Gasmi-Seabrook & N. Joly & M. Poteau & G. Velez-Aguilera & O. Gavet & A. C, 2021. "Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
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