Cell cycle regulation by the ubiquitin pathway

In the past 2 years, two ubiquitin‐dependent proteolytic pathways have been established as important players in the regulation of the cell division cycle. In S. cerevisiae, the entry into S phase requires ubiquitin‐mediated degradation of a cdk inhibitor, p40 Sic1 , in a pathway that involves the E2 enzyme Cdc34. Recent studies reviewed herein show that the Cdc34 pathway targets phosphorylated substrates. A second pathway that regulates chromosome segregation and mitotic exit by degrading anaphase inhibitors and mitotic cyclins involves a different E2 and a large molecular weight E3 complex, called the anaphase‐promoting complex or cyclosome. This pathway targets substrates containing one or more destruction box motif.—Pagano, M. Cell cycle regulation by the ubiquitin pathway. FASEB J. 11, 1067–1075 (1997)