Ubiquitylation and cancer development

Abstract

Ubiquitylation is an essential cellular process, and yet many cancer cells appear to be more reliant upon it than normal cells as they are surprisingly sensitive to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated in vivo. Several reviews have suggested that specific protein targets account for PI induced cell death, but fail to adequately explain why cancer cells are more sensitive than normal cells to PIs. We review the evidence for these models, focusing primarily on inducers of cell death including p53 and the pro-apoptotic Bcl-2 Homology proteins (BH3 proteins) and propose an additional hypothesis; that a tumour cell's abnormal physiology makes it particularl..