Regulated protein degradation has emerged as a
key recurring theme in multiple aspects of cell-cycle
regulation. Importantly, the irreversible nature of
proteolysis makes it an invaluable complement to
the intrinsically reversible regulation through phosphorylation
and other post-translational modifications.
Consequently, ubiquitin-protein ligases, the
protagonists of regulated protein destruction, have
gained prominence that compares to that of the
cyclin-dependent kinases (Cdks) in driving the
eukaryotic cell-cycle clock. This review will focus on
the two main players, the related ubiquitin-protein
ligases APC/C and SCF, and how they control cellcycle
progression. I will also try to delineate the regulation
and interplay of these destruction
mechanisms, which are intricately connected to the
kinase network as well as to extrinsic signals. Moreover,
cell-cycle ubiquitin-protein ligases are themselves
subject to proteolytic control in cis as well as
in trans. Finally, a careful comparison of the functions
and regulation of APC/C and SCF shows that,
in certain aspects, their logic of action is fundamentally
different.