Proteasome inhibition: mechanism of action.

The ubiquitin-proteasome pathway plays a significant role in neoplastic growth and metastasis. The proteasome is responsible for most intracellular protein degradation and regulates numerous cellular functions. Aberrations in cell cycle control caused by altered levels of specific cell-cycle related proteins may lead to oncogenesis. Dysregulation of NF-kappaB signaling also is common to many malignancies and is one of the critical pathways affected by proteasome inhibition. The proteasome structure, in the context of the ubiquitin-proteasome pathway, is discussed. Proteasome inhibitors, such as bortezomib, have the potential to target specific protein substrates, leading to decreased tumor cell growth and increased apoptosis.