Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP:: tipping the scales of cancer

The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation - through the activity of cyclin-dependent kinases (CDKs) - and protein degradation, which occurs through ubiquitin ligases such as SCF (SKP1 - CUL1 - F-box protein) complexes and APC/C (anaphase-promoting complex/cyclosome). Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and beta-TrCP (beta-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.