roughex Down-regulates G₂ cyclins in G₁

Cell cycle arrest in G₁ at the onset of patterning in the Drosophila eye is mediated by roughex. In roughex mutants, cells accumulate Cyclin A protein in early G₁ and progress into g phase precociously. When Roughex is overexpressed in S/G₂ cells, Cyclin A is mislocalized to the nucleus and degraded, preventing mitosis. Whereas Roughex inhibits Cyclin A accumulation, Cyclin E down-regulates Roughex protein in vivo. Roughex binds to Cyclin E and is a substrate for a Cyclin E-Cdk complex in vitro. These data argue that Roughex inhibits Cyclin A accumulation in early G₁ by targeting Cyclin A for destruction. In late G₁, Roughex is destabilized in a Cyclin E-dependent process, releasing Cyclin A for its role in S/G₂.