CDK1 couples proliferation with protein synthesis

Haneke, K.; Schott, J.; Lindner, D.; Hollensen, A. K.; Damgaard, C. K.; Mongis, C.; Knop, M.; Palm, W.; Ruggieri, A.; Stoecklin, G.

doi:10.1101/816850

bioRxiv · 10.1101/816850

CDK1 couples proliferation with protein synthesis

Haneke, K.·Schott, J.·Lindner, D.·Hollensen, A. K.·Damgaard, C. K.·Mongis, C.·Knop, M.·Palm, W.·Ruggieri, A.·Stoecklin, G.

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Abstract

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 extra-mitotic function of CDK1. Dephosphorylation of eIF2 and S6K1 signaling were found to act downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5TOP mRNAs, which includes mRNAs encoding for ribosomal proteins and several translation factors. This effect requires the 5TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Taken together, our results show that CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

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Haneke, K., Schott, J., Lindner, D., Hollensen, A. K., Damgaard, C. K., Mongis, C., Knop, M., Palm, W., Ruggieri, A., Stoecklin, G.. 2019-10-24. CDK1 couples proliferation with protein synthesis. https://doi.org/10.1101/816850

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