Critical cellular processes are regulated, in part, by maintaining the 
appropriate intracellular levels of proteins. Whereas de novo protein synthesis 
is a comparatively slow process, proteins are rapidly degraded at a rate 
compatible with the control of cell cycle transitions and cell death induction. 
A major pathway for protein degradation is initiated by the addition of multiple 
76-amino acid ubiquitin monomers via a three-step process of ubiquitin 
activation and substrate recognition. Polyubiquitination targets proteins for 
recognition and processing by the 26S proteasome, a cylindrical organelle that 
recognizes ubiquitinated proteins, degrades the proteins, and recycles 
ubiquitin. The critical roles played by ubiquitin-mediated protein turnover in 
cell cycle regulation makes this process a target for oncogenic mutations. 
Oncogenes of several common malignancies, for example colon and renal cell 
cancer, code for ubiquitin ligase components. Cervical oncogenesis by human 
papillomavirus is also mediated by alteration of ubiquitin ligase pathways. 
Protein degradation pathways are also targets for cancer therapy, as shown by 
the successful introduction of bortezomib, an inhibitor of the 26S proteasome. 
Further work in this area holds great promise toward our understanding and 
treatment of a wide range of cancers.