There's the Rub: a novel ubiquitin-like modification linked to cell cycle regulation

Abstract

Covalent attachment of the polypeptide ubiquitin to intracellular proteins is achieved through an intricate and highly conserved enzymatic pathway that is beginning to be understood in some detail (for review, see Wilkinson 1995; Hochstrasser 1996; Pickart 1997). Ubiquitin is joined reversibly to proteins by an isopeptide linkage of the carboxy-terminal carboxyl group of ubiquitin to lysine side chains of the acceptor proteins (Fig. 1). In the majority of cases examined, the modified protein, particularly when it is attached to multiple ubiquitin molecules, is targeted to a large, abundant intracellular protease called the proteasome, which degrades the substrate into small peptides but allows recycling of the ubiquitin moieties. Over the past few years, it has emerged that eukaryotes also express a set of ubiquitin-like proteins (Ubls) that are significantly diverged from ubiquitin itself yet are also ligated to other proteins (Haas and Siepmann 1997; Johnson and Hochstrasser 1997). The reactions involving these variants appear to have much in common with those of ubiquitin, but the Ubls have novel regulatory functions not necessarily linked to proteolysis. In this issue, Lammer et al. describe an unexpected connection between a Ubl called Rub1 (related to ubiquitin 1) from the yeast Saccharomyces cerevisiae and a ubiquitin–protein ligase complex that is critical for progression from G1 to S phase in the cell cycle. In this commentary, I will discuss these new results together with recent related developments on the mechanisms and functions of Ubl–protein ligation.