THE UBIQUITIN SYSTEM

The selective degradation of many short-lived proteins in eukaryotic c ells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a hig hly conserved small protein. Ubiquitin-mediated degradation of regulat ory proteins plays important roles in the control of numerous processe s, including cell-cycle progression, signal transduction, transcriptio nal regulation, receptor down-regulation, and endocytosis. The ubiquit in system has been implicated in the immune response, development, and programmed cell death. Abnormalities in ubiquitin-mediated processes have been shown to cause pathological conditions, including malignant transformation. In this review we discuss recent information on functi ons and mechanisms of the ubiquitin system. Since the selectivity of p rotein degradation is determined mainly at the stage of ligation to ub iquitin, special attention is focused on what we know, and would like to know, about the mode of action of ubiquitin-protein ligation system s and about signals in proteins recognized by these systems.