APC/C and SCF: controlling each other and the cell cycle.
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 cell-cycle 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.
Vodermaier
Hartmut C
HC
Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. vodermaier@imp.univie.ac.at
D064173:Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000502:physiology*; D005057:Eukaryotic Cells / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*; D014452:Ubiquitins / Q000502:physiology*
D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases