ROUGHEX DOWN-REGULATES G(2) CYCLINS IN G(1)

Cell cycle arrest in G(1) at the onset of patterning in the Drosophila eye is mediated by rougher. In rougher mutants, cells accumulate Cycl in A protein in early G(1) and progress into S phase precociously. Whe n Rougher is overexpressed in S/G(2) cells, Cyclin A is mislocalized t o the nucleus and degraded, preventing mitosis. Whereas Rougher inhibi ts Cyclin A accumulation, Cyclin E down-regulates Rougher protein in v ivo. Rougher binds to Cyclin E and is a substrate for a Cyclin E-Cdk c omplex in vitro. These data argue that Rougher inhibits Cyclin A accum ulation in early G(1) by targeting Cyclin A for destruction. In late G (1), Rougher is destabilized in a Cyclin E-dependent process, releasin g Cyclin A for its role in S/G(2).