The cAMP-PKA signaling initiates mitosis by phosphorylating Bora

Min Zhu, Shinan Zhou, Yingqi Zhang, Qinfu Chen, Xueying Yuan, Long Zhang, Haiyan Yan () and Fangwei Wang ()
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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

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63352-y

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