title: Proteasomes: a complex story.
abstract: Protein degradation in eukaryotic cells is important for regulation of metabolism, progression through the division cycle, in cell signalling pathways, and in mammals also for generation of antigen fragments for presentation on the major histocompatibility complex (MHC) class I. Most cell proteins are degraded via the ubiquitin/proteasome pathway where an elaborate enzyme system recognises the protein substrates and marks them for destruction by attachment of a chain of ubiquitin. The substrates are then bound to 26S proteasomes, unfolded, and threaded into the cylindrical central part of the 26S proteasome, where they are cleaved to peptides. Recently many proteins, which associate with proteasomes, have been found. One of them controls the cellular contents of proteasomes by regulating their synthesis. Others ubiquitylate substrates or transfer substrates to proteasomes. Others again seem to unfold the substrates or release ubiquitin and glycans from them during degradation, stabilise proteasomes, regulate their cellular localisation, and modify their activity. It therefore appears that proteasomes are centres in macromolecular clusters, which degrade cell proteins in a tightly regulated manner.
authors.affiliation: August Krogh Institute, Universitetsparken 13, DK-2100 Copenhagen O, Denmark. KBHendil@aki.ku.dk
authors.forename: Klavs B
authors.initials: KB
authors.lastname: Hendil
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D015398:Signal Transduction; D013379:Substrate Specificity; D014452:Ubiquitins / Q000737:chemistry*
chemical_list: D009097:Multienzyme Complexes; D014452:Ubiquitins; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease