title: The ubiquitin-mediated proteolytic pathway.
abstract: Ubiquitin modification of a variety of protein targets within the cell plays important roles in many cellular processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, and biogenesis of mitochondria and ribosomes. The best studied modification occurs in the ubiquitin-dependent proteolytic pathway. Degradation of a protein by the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP-dependent mode to the protein substrate. The protein moiety of the conjugate is then degraded by a specific protease into free amino acids with the release of free and reutilizable ubiquitin. This process also requires energy. In addition, stable mono-ubiquitin adducts are also found intracellularly, for example, those involving nucleosomal histones. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, very little is known about the cellular substrates of the system and the signals that target them for conjugation and degradation. The scope of this review is to summarize briefly what is currently known on the role of the ubiquitin system in protein turnover, and to discuss in detail the mechanisms involved in selection of substrates for conjugation and in degradation of ubiquitin-conjugated proteins.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
authors.forename: A
authors.initials: A
authors.lastname: Ciechanover
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008025:Ligases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D011506:Proteins; D014452:Ubiquitins; D010450:Endopeptidases; D008025:Ligases