The role of the ubiquitin-proteasome pathway in apoptosis.
Coordinated intracellular protein degradation mediated by the ubiquitin-proteasome pathway is crucial to a vast array of cellular processes including orderly progression through the mitotic cycle. Similarly important to both the fates of individual cells, as well as to the normal function of multicellular organisms, is the process of apoptosis, or programmed cell death. Execution of this latter process has been known for some time to be intimately associated with the activity of caspases, a family of proteases related to interleukin-1-beta-converting enzyme. Evidence is now accumulating, however, that the ubiquitin-proteasome system itself plays an important role in apoptosis, and some of the cellular pathways that are impacted upon by the proteasome, and may lead to apoptosis, are beginning to be dissected. This review provides a summary of the experimental basis by which components of the ubiquitin-proteasome pathway have been linked to apoptosis, and attempts are made to formulate a hypothesis about its role in this process.
Orlowski
R Z
RZ
The Department of Medicine, Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. R_Orlowski@med.unc.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology; D014452:Ubiquitins / Q000378:metabolism*
D009097:Multienzyme Complexes; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex