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CDK1 and calcineurin regulate Maskin association with eIF4E and translational control of cell cycle progression

Nature Structural & Molecular Biology volume 13, pages 1128–1134 (2006)Cite this article

Abstract

Maskin regulates assembly of the eIF4F translation initiation complex on messenger RNAs that contain cytoplasmic polyadenylation elements (CPEs) in their 3′ untranslated regions. Because Maskin and eIF4G contain similar peptide motifs that bind eIF4E, they compete for occupancy of this factor and consequently control translation. One mRNA that is regulated by Maskin encodes cyclin B1, whose translation oscillates with the early cell cycles of Xenopus laevis embryos. Here we show that Maskin phosphorylation-dephosphorylation also oscillates with the cell cycle and is controlled by the kinase CDK1 and the phosphatase calcineurin. These phosphorylation events control the Maskin-eIF4E interaction and, as a result, translation of cyclin B1 mRNA. Cell cycle progression requires this Maskin-mediated translational regulation.

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Figure 1: Maskin interaction with eIF4E oscillates with the cell cycle.
Figure 2: Maskin phosphorylation oscillates with the cell cycle.
Figure 3: Two-dimensional phosphopeptide maps of Maskin during the cell cycle.
Figure 4: Calcineurin interacts with thiophosphorylated Maskin.
Figure 5: CaN controls Maskin phosphorylation and interaction with eIF4E.
Figure 6: Model for oscillating translation during the early Xenopus cell cycles.

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Acknowledgements

We thank D. Barnard for technical advice and generously supplying some reagents and B. Neel for making us aware of the affinity chromatography method using thiophosphorylated peptides. This work was supported by grants from the US National Institutes of Health. Core support from the Diabetes and Endocrine Research Center Program Project is gratefully acknowledged.

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  1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, 01605, Massachusetts, USA

    Quiping Cao, Jong Heon Kim & Joel D Richter

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  1. Quiping Cao
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  2. Jong Heon Kim
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  3. Joel D Richter
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Contributions

Q.C. performed all the experiments, J.H.K. generated some of the mutant Maskin proteins, Q.C. and J.D.R. designed the experiments and analyzed the data and J.D.R. wrote the paper.

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Correspondence to Joel D Richter.

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The authors declare no competing financial interests.

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Cao, Q., Kim, J. & Richter, J. CDK1 and calcineurin regulate Maskin association with eIF4E and translational control of cell cycle progression. Nat Struct Mol Biol 13, 1128–1134 (2006). https://doi.org/10.1038/nsmb1169

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