TY - JOUR
T1 - Posttranslational control of Cdc25 degradation terminates drosophila's early cell-cycle program
AU - Di Talia, Stefano
AU - She, Richard
AU - Blythe, Shelby A.
AU - Lu, Xuemin
AU - Zhang, Qi Fan
AU - Wieschaus, Eric F.
N1 - Funding Information:
We thank the Drosophila Genomics Resource Center for plasmids and the Bloomington Drosophila Stock Center for fly stocks. We thank Oliver Grimm and Reba Samanta for help with experiments. We thank Jeff Farrell and Pat O’Farrell for discussion. This work was in part supported by the National Institutes of Health (NICHD grant 5R37HD15587 to E.F.W. and NRSA postdoctoral fellowship 1F32HD072653 to S.A.B.). S.D. was a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. E.F.W. is an investigator of the Howard Hughes Medical Institute.
PY - 2013/1/21
Y1 - 2013/1/21
N2 - 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.
AB - 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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U2 - 10.1016/j.cub.2012.11.029
DO - 10.1016/j.cub.2012.11.029
M3 - Article
C2 - 23290553
AN - SCOPUS:84872676237
SN - 0960-9822
VL - 23
SP - 127
EP - 132
JO - Current Biology
JF - Current Biology
IS - 2
ER -