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Posttranslational Control of Cdc25 Degradation Terminates Drosophila's Early Cell-Cycle Program

Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Current biology: CB (Impact Factor: 9.92). 12/2012; 23(2). DOI: 10.1016/j.cub.2012.11.029
Source: PubMed

ABSTRACT In most metazoans, early embryonic development is characterized by rapid mitotic divisions that are controlled by maternal mRNAs and proteins that accumulate during oogenesis [1]. These rapid divisions pause at the midblastula transition (MBT), coinciding with a dramatic increase in gene transcription and the degradation of a subset of maternal mRNAs [2, 3]. In Drosophila, the cell-cycle pause is controlled by inhibitory phosphorylation of Cdk1, which in turn is driven by downregulation of the activating Cdc25 phosphatases [4, 5]. Here, we show that the two Drosophila Cdc25 homologs, String and Twine, differ in their dynamics and that, contrary to current models [4], their downregulations are not controlled by mRNA degradation but through different posttranslational mechanisms. The degradation rate of String protein gradually increases during the late syncytial cycles in a manner dependent on the nuclear-to-cytoplasmic ratio and on the DNA replication checkpoints. Twine, on the other hand, is targeted for degradation at the onset of the MBT through a switch-like mechanism controlled, like String, by the nuclear-to-cytoplasmic ratio, but not requiring the DNA replication checkpoints. We demonstrate that posttranslational control of Twine degradation ensures that the proper number of mitoses precede the MBT.

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    • "However, at present it is not clear what role the nucleus to cytoplasm ratio plays in regulating the cell cycle changes in Drosophila. The studies by the Wieschaus and O'Farrell groups indicate that the nucleus to cytoplasm ratio triggers the onset of transcription of the genes required for Twine destruction (Di Talia et al., 2013; Farrell and O'Farrell, 2013). The study by the Großhans group, however, suggests that the destruction of Twine occurs independently of changes to the nucleus to cytoplasm ratio (Sung et al., 2013). "
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    ABSTRACT: Three recent studies revise the prevailing view of regulation of the mid-blastula transition in Drosophila, indicating particular requirements for the Cdc25 phosphatase Twine and for zygotic transcription of a specific set of genes.
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