THE UBIQUITIN-CONJUGATION SYSTEM

The ubiquitin/proteasome system is believed to be the major nonlysosomal proteolytic system of eukaryotic cells. It is present in the cytosol and the nucleus but apparently absent from the lumen of membrane-enclosed organelles, i. e., the endoplasmic reticulum, the Golgi and vesicular system, mitochondria, chloroplasts, and peroxisomes (for reviews see Finley and Chau, 1991; Jentsch, 1992a,b; Hershko and Ciechanover, 1992; Ciechanover, 1994; Hochstrasser, 1995; Smith et al., 1996). Substrates of this pathway include soluble proteins, subunits of oligomeric protein complexes, and integral membrane proteins. An important function of this pathway is the elimination of abnormal proteins (e. g., misfolded, misassembled) generated under normal and, in particular, stress conditions. Moreover, it is assumed that most naturally short-lived proteins of the cytosol and the nucleus are degraded by this pathway. Known substrates include proteins with important regulatory roles such as transcription factors, cell cycle regulators, and signal transducers.