Protein modification via covalent attachment of ubiquitin has emerged as one of the most common regulatory processes in all eukaryotes; it is possibly second only to phosphorylation. In fact, ubiquitination and phosphorylation have much in common: both occur rapidly-often in response to an extracellular signal-and both are quickly reversed by a large set of dedicated enzymes termed deubiquitination enzymes and phosphatases, respectively. In addition, these two protein-modification events often cooperate in mobilizing a particular cellular pathway. Traditionally, ubiquitination has been associated with proteolytic events, mostly in conjunction with the 26S proteosome. Recently, however, ubiquitination has been implicated in other regulatory mechanisms. Some involve proteosome-independent protein degradation, whereas others are entirely proteolysis-independent, ranging from protein kinase activation to translation control. Therefore, it is not surprising that the ever-evolving immune system is an excellent mirror for the multiple roles played by ubiquitination within an organism.
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Acknowledgements I thank members of my laboratory,A. Ciechanover and A. Mahler for helpful comments on the manuscript. Supported by the Israel Science Foundation; funded by the Israel Academy for Sciences and Humanities-Centers of Excellence Program, the German-Israeli Program (DIP) and the European Community (5th Framework).