Twine Degradation and Cell Cycle Control in Early Drosophila Development

Abstract

The mid-blastula transition (MBT), an important milestone in Drosophila melanogaster development, marks the shift from maternal to zygotic gene control of embryogenesis, the loss of cell division synchrony, and the addition of gap stages to the cell cycle. Previous studies have demonstrated that the degradation of Twine, a Cdc25 phosphatase, results in the initiation of the MBT. In fact, Twine is subjected to a posttranslational modification that leads to protein down-regulation. To understand more about Twine degradation, we initiated a two-pronged approach: (1) the identification of the degradation sequence (degron) which, upon post-translational modifications through MBT-specific signals, causes Twine instability and (2) the identification of the factor that initiates Twine degradation at the onset of MBT. Through live imaging analysis of mutant embryos carrying deletions of Twine, we determined that this degron resides between the 106th and 150th amino acid. The mechanism contributing to Twine instability is unlikely to require protein phosphorylation. Through immunoflouroscence staining of compound chromosome embryos, we proposed that a key factor(s) promoting Twine degradation resides on the left arm of the third chromosome. A clear understanding of Twine degradation is essential because over-expression of Cdc25 phosphatase is prevalent in many forms of cancer.