Ubiquitin-mediated proteolysis: biological regulation via destruction

The ubiquitin proteolytic system plays an important role in a broad array o f basic cellular processes. Among these are regulation of cell cycle, modul ation of the immune and inflammatory responses, control of signal transduct ion pathways, development and differentiation. These complex processes are controlled via specific degradation of a single or a subset of proteins. De gradation of a protein by the ubiquitin system involves two successive step s, conjugation of multiple moieties of ubiquitin and degradation of the tag ged protein by the 26S proteasome. An important question concerns the ident ity of the mechanisms that underlie the high degree of specificity of the s ystem. Substrate recognition is governed by a large family ubiquitin ligase s that recognize the substrates, bind them and catalyze/facilitate their in teraction with ubiquitin. BioEssays 22:442-451, 2000. (C) 2000 John Wiley & Sons, Inc.