AMPKα2 activation by an energy-independent signal ensures chromosomal stability during mitosis
Jianlin Lu,
Yuanyuan Huang,
Li Zhan,
Ming Wang,
Leilei Xu,
McKay Mullen,
Jianye Zang,
Guowei Fang,
Zhen Dou,
Xing Liu,
Wei Liu,
Minerva Garcia-Barrio,
Xuebiao Yao
Affiliations
Jianlin Lu
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, CAS Center for Excellence in Molecular Cell Science & Hefei National Science Center for Physical Sciences at Microscale, Hefei, Anhui 230026, China
Yuanyuan Huang
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, CAS Center for Excellence in Molecular Cell Science & Hefei National Science Center for Physical Sciences at Microscale, Hefei, Anhui 230026, China
Li Zhan
Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, 230027 Anhui, China
Ming Wang
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, CAS Center for Excellence in Molecular Cell Science & Hefei National Science Center for Physical Sciences at Microscale, Hefei, Anhui 230026, China
Leilei Xu
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China
McKay Mullen
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China
Jianye Zang
Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, 230027 Anhui, China
Guowei Fang
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China
Zhen Dou
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, CAS Center for Excellence in Molecular Cell Science & Hefei National Science Center for Physical Sciences at Microscale, Hefei, Anhui 230026, China
Xing Liu
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, CAS Center for Excellence in Molecular Cell Science & Hefei National Science Center for Physical Sciences at Microscale, Hefei, Anhui 230026, China; Corresponding author
Wei Liu
Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Corresponding author
Minerva Garcia-Barrio
University of Michigan, Ann Arbor, MI 48108, USA; Corresponding author
Xuebiao Yao
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China; Corresponding author
Summary: AMP-activated protein kinase (AMPK) senses energy status and impacts energy-consuming events by initiating metabolism regulatory signals in cells. Accumulating evidences suggest a role of AMPK in mitosis regulation, but the mechanism of mitotic AMPK activation and function remains elusive. Here we report that AMPKα2, but not AMPKα1, is sequentially phosphorylated and activated by CDK1 and PLK1, which enables AMPKα2 to accurately guide chromosome segregation in mitosis. Phosphorylation at Thr485 by activated CDK1-Cyclin B1 brings the ST-stretch of AMPKα2 to the Polo box domain of PLK1 for subsequent Thr172 phosphorylation by PLK1. Inserting of the AMPKα2 ST-stretch into AMPKα1, which lacks the ST-stretch, can correct mitotic chromosome segregation defects in AMPKα2-depleted cells. These findings uncovered a specific signaling cascade integrating sequential phosphorylation by CDK1 and PLK1 of AMPKα2 with mitosis to maintain genomic stability, thus defining an isoform-specific AMPKα2 function, which will facilitate future research on energy sensing in mitosis.
