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Review

Nature Reviews Cancer 8, 438–449 (1 June 2008) | doi:10.1038/nrc2396

Deregulated proteolysis by the F-box proteins SKP2 and |[beta]|-TrCP: tipping the scales of cancer

David Frescas & Michele Pagano

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 β-TrCP (β-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.