A DEVELOPMENTAL TIMER REGULATES DEGRADATION OF CYCLIN E1 AT THE MIDBLASTULA TRANSITION DURING XENOPUS EMBRYOGENESIS

We have analyzed cyclin E1, a protein that is essential for the G(1)/S transition, during early development in Xenopus embryos, Cyclin E1 wa s found to be abundant in eggs, and after fertilization, until the mid blastula transition (MET) when levels of cyclin E1 protein, and associ ated kinase activity, were found to decline precipitously, Our results suggest that the reduced level of the cyclin E1 protein detected afte r the MBT does not occur indirectly as a result of degradation of the maternally encoded cyclin E1 mRNA, Instead, the stability of cyclin E1 protein appears to play a major role in reduction of cyclin E1 levels at this time, Cyclin E1 protein was found to be stable during the cle avage divisions but degraded with a much shorter half-life after the M ET. Activation of cyclin E1 protein turnover occurs independent of cel l cycle progression, does not require ongoing protein synthesis, and i s not triggered as a result of the ratio of nuclei to cytoplasm in emb ryonic cells that initiates the MET. We therefore propose that a devel opmental timing mechanism measures an approximate to 5-hr time period, from the time of fertilization, and then allows activation of a prote in degradative pathway that regulates cyclin E1, Characterization of t he timer suggests that it might be held inactive in eggs by a mitogen- activated protein kinase signal transduction pathway.