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Beskrivelse
The ubiquitin system has two major functions in eukaryotic cells: it r- ulates protein degradation, which is essential for normal cellular fu- tion and for the removal of potentially harmful, damaged, or misfolded proteins, and it controls protein activity by regulating protein-protein interactions and subcellullar localization. The ubiquitin system is thus involved in processes as diverse as cell cycle progression, signal tra- duction, gene transcription, and DNA repair. Not surprisingly, defects in the ubiquitin system have been linked with numerous diseases such as cancer, in?ammation, central nervous system disorders, and metabolic dysfunction. Ubiquitin is a highly conserved 76-amino acid protein which is transferred to its target protein in an ATP-dependent manner. This post-translational modi?cation takes place in a hierarchical, three-step fashion involving an E1 ubiquitin-activating enzyme, an E2 ubiquit- conjugating enzyme, and an E3 ubiquitin ligase. Substrate speci?city is predominantly controlled by members of a large family of E3 - zymes, which form complexes with the proteins that will be modi?ed.This ultimately leads to the covalent attachment of the C-terminus of ubiquitin to usually an?-amino group of a lysine residue in the targeted protein. Additional ubiquitin transfer to lysine-48 of ubiquitin itself will form a polyubiquitin chain, which usually targets the conjugate for degradation by the proteasome. By contrast, mono- or polyubiquityla- VI Preface tion involving lysine-63 is normally involved in the control of protein activity. Ubiquitylation can be reverted by deubiquitylating enzymes, of which approximately 95 exist in mammals.
