ABSTRACT

F or several years, most o f the publications in the ubiquitin field began by accentuating the evolutionary conservation of the basic unit of the system, the polypeptide ubiquitin (Ub): ubiquitin is a highly conserved polypeptide of 76 amino acids found in all eukaryotic cells. Of course this is still true, but it is now widely accepted that Ub serves a fundamental and evolutionary conserved function in the major proteolytic pathway of eukaryotic cells, the ubiquitinproteasome pathway. Ub itself has no enzy­ matic activity but when it is covalently linked to other proteins it functions as a tag, marking proteins for destruction by the 26S proteasome.1'3 Substrates for ubiquitination are abnormal or structurally distorted proteins, but most importantly the system selectively destroys cellular regulators many of which are short-lived. Degradation of these substrates often occurs in response to specific signals or at certain time points in the cell cycle. Moreover, short-lived regulators may form complexes w ith other, stable proteins. Consequently, the differentiation of short­ lived substrates from long-lived proteins must be extremely precise. How this accuracy is achieved is the central question of the research in this area and the answer is found in the conjugation m achinery recognizing the proteolytic substrates. The knowledge on these enzymes will be summarized in the following

Chapter. Another subject that will be discussed are the recently identified proteins that display s im ilarities to Ub (U bl, ub iqu itin -like proteins). Like ubiquitin, some of them are covalently linked to a number of cellular proteins and the enzymatic activities required for this modification parallel those linking Ub to substrates.4,5 Because the Ubls have been described only recently, their function is less clear. But from the current knowledge it can be speculated that Ubl-conjugation is not direcdy linked to proteolysis (see below). It can be speculated that these homologues expand the functional repertoire of the system.