Cell cycle, proteolysis and cancer.

Research in the past 15 years has shown that the mammalian cell cycle is controlled by the action of cyclin-dependent kinases (CDKs). A crucial substrate of the CDKs in G1-phase is the retinoblastoma tumor suppressor (pRB), which restrains proliferation largely by repressing the activity of the E2F transcription factors. More recent work has shown that the cell cycle is also a tale of two classes of ubiquitin ligases, referred to as SCF and APC/C ligases. CDKs, E2F and ubiquitin ligases reciprocally regulate each other, resulting in complex feedback loops. Perturbation of this network of molecular machines is associated with proliferative diseases, including cancer.