title: The proteasome.
abstract: The proteasome is an abundant multicatalytic enzyme complex present in the cytoplasm and nucleus of all eukaryotic cells. The primary function of the proteasome is to degrade proteins. While it was once thought to act primarily as a cellular "garbage disposal" that removed damaged or misfolded proteins from cells, the proteasome is now known to also remove various short-lived proteins that regulate the cell cycle, cell growth, and differentiation. By regulating the turnover of these proteins via timely degradation and recycling, the proteasome plays a critical role in the maintenance of cellular homeostasis. Substrates of the proteasome include cell-cycle regulators, signaling molecules, tumor suppressors, transcription factors, and antiapoptotic proteins; over 80% of all cellular proteins are recycled through the proteasome. This article discusses the structure and function of the proteasome, and its role in malignant cells and as a therapeutic target.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Dalton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002448:Cell Adhesion; D019008:Drug Resistance, Neoplasm; D006412:Hematopoietic Stem Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011719:Pyrazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D000069286:Bortezomib; D011480:Protease Inhibitors; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011719:Pyrazines; D000097782:NF-kappaB-Inducing Kinase