Cdc20 protein contains a destruction-box but, unlike Clb2, its proteolysisis not acutely dependent on the activity of anaphase-promoting complex

Both chromosome segregation and the final exit from mitosis require a ubiqu itin-protein ligase called anaphase-promoting complex (APC) or cyclosome. T his multiprotein complex ubiquitinates various substrates, such as the anap hase inhibitor Pds1. and mitotic cyclins, and thus targets them for proteol ysis by the 26S proteasome. The ubiquitination by APC is dependent on the p resence of a destruction-box sequence in the N-terminus of target proteins. Recent reports have strongly suggested that Cdc20,a WD40 repeat-containing protein required for nuclear division in the budding yeast Saccharomyces c erevisiae, is essential for the APC-mediated proteolysis. To understand the function of CDC20, we have studied its regulation in some detail. The expr ession of the CDC20 gene is cell-cycle regulated such that it is transcribe d only during late S phase and mitosis. Although the protein is unstable to some extent through out the cell cycle, its degradation is particularly en hanced in G1. Cdc20 contains a destruction box sequence which, when mutated or deleted, stabilizes it considerably in G1. Surprisingly, we find that w hile the inactivation of APC subunits Cdc16, Cdc23 or Cdc27 results in stab ilization of the mitotic cyclin Clb2 in G1, the proteolytic destruction of Cdc20 remains largely unaffected. This suggests the existence of proteolyti c mechanisms in G1 that can degrade destruction-box containing proteins, su ch as Cdc20, in an APC-independent manner.