Tuning the proteasome to brighten the end of the journey.
Degradation by the proteasome is the fate for a large portion of cellular proteins, and it plays a major role in maintaining protein homeostasis, as well as in regulating many cellular processes like cell cycle progression. A decrease in proteasome activity has been linked to aging and several age-related neurodegenerative pathologies and highlights the importance of the ubiquitin proteasome system regulation. While the proteasome has been traditionally viewed as a constitutive element of proteolysis, major studies have highlighted how different regulatory mechanisms can impact its activity. Importantly, alterations of proteasomal activity may have major impacts for its function and in therapeutics. On one hand, increasing proteasome activity could be beneficial to prevent the age-related downfall of protein homeostasis, whereas inhibiting or reducing its activity can prevent the proliferation of cancer cells.
Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, Vancouver, Canada; mayor@mail.ubc.ca.
Thibault
T
Mayor
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel; and.
Michal
M
Sharon
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Michael H
MH
Glickman
D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D046988:Proteasome Endopeptidase Complex
UPS; proteasome; proteolysis; ubiquitin