Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopusoocytes.

The c-Mos proto-oncogene product plays an essential role during meiotic div isions in vertebrate eggs. In Xenopus, it is required for progression of oo cyte maturation and meiotic arrest of unfertilized eggs. Its degradation af ter fertilization is essential to early embryogenesis. In this study we inv estigated the mechanisms involved in c-Mos degradation. We present in vivo evidence for ubiquitin-dependent degradation of c-Mos in activated eggs. We found that c-Mos degradation is not directly dependent on the anaphase-pro moting factor activator Fizzy/cdc20 but requires cyclin degradation. We dem onstrate that cyclin B/cdc2 controls in vivo c-Mos phosphorylation and stab ilization. Moreover, we show that cyclin B/cdc2 is capable of directly phos phorylating c-Mos in vitro, inducing a similar mobility shift to the one ob served in vivo. Tryptic phosphopeptide analysis revealed a practically iden tical in vivo and in vitro phosphopeptide map and allowed identification of serine-3 as the largely preferential phosphorylation site as previously de scribed (Freeman et al., 1992). Altogether, these results demonstrate that, in vivo, stability of c-Mos is directly regulated by cyclin B/cdc2 kinase activity.