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CDK1 couples proliferation with protein synthesis

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DOI

  • Katharina Haneke, Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg, Germany.
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  • Johanna Schott, Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg, Germany.
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  • Doris Lindner, Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg, Germany.
  • ,
  • Anne Kruse Hollensen
  • Christian Kroun Damgaard
  • Cyril Mongis, Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg, Germany.
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  • Michael Knop, Cell Morphogenesis and Signal Transduction, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
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  • Wilhelm Palm, Cell Signaling and Metabolism, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
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  • Alessia Ruggieri, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, University of Heidelberg, Heidelberg, Germany.
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  • Georg Stoecklin, Center for Molecular Biology of Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg, Germany.

Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5'TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5'TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

Original languageEnglish
Article numbere201906147
JournalThe Journal of Cell Biology
Volume219
Issue3
Number of pages23
ISSN0021-9525
DOIs
Publication statusPublished - 2020

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