The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box
protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin–proteasome
pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2
(SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to
degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as
Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for
degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis,
prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular
processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug
resistance, and DNA-damage responses.
Keywords: β-TrCP, E3 ligase, F-box protein, FBXW7, human cancer, proteasome, SCF complex, SKP2, ubiquitin.
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