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10 The Yeast Ubiquitin System

Daniel Finley


Ubiquitin is a small protein found in eukaryotic cells either free or covalently joined to a variety of cytoplasmic, nuclear, and integral membrane proteins. Ubiquitination, like phosphorylation, is used in a wide variety of regulatory roles; DNA repair, cell cycle control, and the stress response all require the participation of specific ubiquitinating enzymes. Whereas the phosphorylation of proteins is often used to change their functional state, Ubiquitination appears to serve as a marker that targets a protein for degradation. However, since not all ubiquitinated proteins are selectively degraded, ubiquitin may play nonproteolytic roles as well.

The formation, deubiquitination, and degradation of ubiquitin-protein conjugates each involves a large number of gene products. The elucidation of this complex system requires a combination of genetics and biochemistry for which yeast is ideally suited, and yeast has become the principal model sytem for functional if not mechanistic studies of ubiquitination (for previous reviews, see Finley and Chau 1991; Jentsch 1992; Varshavsky 1992). Because the ubiquitin system is highly conserved in evolution, it has been possible to interpret genetic studies of ubiquitination in yeast in light of enzymological work carried out in mammalian extracts. Therefore, some description of the mammalian work is given in this chapter to provide a more complete framework for discussion.

Ubiquitin is ligated to acceptor proteins through its carboxyl terminus following an initial activation step. In protein substrates, ɛ-amino groups of lysine residues serve as target sites. Thus, the ubiquitin-protein linkage is in the form of...

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