The cAMP-PKA signaling initiates mitosis by phosphorylating Bora
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-d...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63352-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226158259830784 |
|---|---|
| author | Min Zhu Shinan Zhou Yingqi Zhang Qinfu Chen Xueying Yuan Long Zhang Haiyan Yan Fangwei Wang |
| author_facet | Min Zhu Shinan Zhou Yingqi Zhang Qinfu Chen Xueying Yuan Long Zhang Haiyan Yan Fangwei Wang |
| author_sort | Min Zhu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b42f3ca26a2041df830246d5735e36ba |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b42f3ca26a2041df830246d5735e36ba2025-08-24T11:37:15ZengNature PortfolioNature Communications2041-17232025-08-0116111810.1038/s41467-025-63352-yThe cAMP-PKA signaling initiates mitosis by phosphorylating BoraMin Zhu0Shinan Zhou1Yingqi Zhang2Qinfu Chen3Xueying Yuan4Long Zhang5Haiyan Yan6Fangwei Wang7Department of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversitySchool of Medicine, Hangzhou City UniversityDepartment of Gynecologic Oncology, Women’s Hospital, School of Medicine and MOE Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang UniversityAbstract 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.https://doi.org/10.1038/s41467-025-63352-y |
| spellingShingle | Min Zhu Shinan Zhou Yingqi Zhang Qinfu Chen Xueying Yuan Long Zhang Haiyan Yan Fangwei Wang The cAMP-PKA signaling initiates mitosis by phosphorylating Bora Nature Communications |
| title | The cAMP-PKA signaling initiates mitosis by phosphorylating Bora |
| title_full | The cAMP-PKA signaling initiates mitosis by phosphorylating Bora |
| title_fullStr | The cAMP-PKA signaling initiates mitosis by phosphorylating Bora |
| title_full_unstemmed | The cAMP-PKA signaling initiates mitosis by phosphorylating Bora |
| title_short | The cAMP-PKA signaling initiates mitosis by phosphorylating Bora |
| title_sort | camp pka signaling initiates mitosis by phosphorylating bora |
| url | https://doi.org/10.1038/s41467-025-63352-y |
| work_keys_str_mv | AT minzhu thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT shinanzhou thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT yingqizhang thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT qinfuchen thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT xueyingyuan thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT longzhang thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT haiyanyan thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT fangweiwang thecamppkasignalinginitiatesmitosisbyphosphorylatingbora AT minzhu camppkasignalinginitiatesmitosisbyphosphorylatingbora AT shinanzhou camppkasignalinginitiatesmitosisbyphosphorylatingbora AT yingqizhang camppkasignalinginitiatesmitosisbyphosphorylatingbora AT qinfuchen camppkasignalinginitiatesmitosisbyphosphorylatingbora AT xueyingyuan camppkasignalinginitiatesmitosisbyphosphorylatingbora AT longzhang camppkasignalinginitiatesmitosisbyphosphorylatingbora AT haiyanyan camppkasignalinginitiatesmitosisbyphosphorylatingbora AT fangweiwang camppkasignalinginitiatesmitosisbyphosphorylatingbora |