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.
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA. teru_hideshima@dfci.harvard.edu
Teru
T
Hideshima
Kenneth C
KC
Anderson
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex