Biologic impact of proteasome inhibition in multiple myeloma cells--from the aspects of preclinical studies.

The ubiquitin-proteasome pathway (UPP) is a major protein degradation system that maintains homeostasis of intracellular proteins, involved in DNA repair, cell cycle regulation, cell proliferation, and drug resistance. Since numerous proteins are processed by proteasomes, their inhibition triggers dramatic disruption of protein homeostasis. Consequently, accumulation of polyubiquitinated proteins triggers different types of cellular stress responses, followed by growth arrest and cytotoxicity. Importantly, multiple myeloma (MM) cells are considered to have lower threshold against these stresses than other cell types, which makes these cells sensitive to proteasome inhibitors.