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The generation of free radicals and the resulting oxidative modification of cell structures are omnipresent in mammalian cells. This includes the permanent oxidation of proteins leading to the disruption of the protein structure and an impaired functionality. In consequence, these oxidized proteins have to be removed in order to prevent serious metabolic disturbances. The most important cellular proteolytic system responsible for the removal of oxidized proteins is the proteasomal system. For normal functioning, the proteasomal system needs the coordinated interaction of numerous components. This review describes the fundamental functions of the 20S  core proteasome, its regulators, and the roles of the proteasomal system beyond the removal of oxidized proteins in mammalian cells. © 2008 IUBMB IUBMB Life, 60(11): 743-752, 2008
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