Cyclin-dependent kinase 1-mediated AMPK phosphorylation regulates chromosome alignment and mitotic progression

Seth Stauffer, Yongji Zeng, Montserrat Santos, Jiuli Zhou, Yuanhong Chen, Jixin Dong

Research output: Contribution to journalArticle

Abstract

AMP-activated protein kinase (AMPK), a heterotrimeric serine/ threonine kinase and cellular metabolic sensor, has been found to regulate cell cycle checkpoints in cancer cells in response to energetic stress, to harmonize proliferation with energy availability. Despite AMPK's emergent association with the cell cycle, it still has not been fully delineated how AMPK is regulated by upstream signaling pathways during mitosis. We report, for the first time, direct CDK1 phosphorylation of both the catalytic α1 and α2 subunits, as well as the β1 regulatory subunit, of AMPK in mitosis. We found that AMPKknockout U2OS osteosarcoma cells have reduced mitotic indexes and that CDK1 phosphorylation-null AMPK is unable to rescue the phenotype, demonstrating a role for CDK1 regulation of mitotic entry through AMPK. Our results also denote a vital role for AMPK in promoting proper chromosomal alignment, as loss of AMPK activity leads tomisaligned chromosomes and concomitant metaphase delay. Importantly, AMPK expression and activity was found to be critical for paclitaxel chemosensitivity in breast cancer cells and positively correlated with relapse-free survival in systemically treated breast cancer patients.

Original languageEnglish (US)
Article numberjcs236000
JournalJournal of cell science
Volume132
Issue number20
DOIs
StatePublished - Jan 1 2019

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Keywords

  • AMPK
  • CDK1
  • Mitotic phosphorylation
  • Taxol sensitivity

ASJC Scopus subject areas

  • Cell Biology

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