title: Mechanisms of protein degradation: an odyssey with ODC.
abstract: Intracellular proteolysis plays an important role in regulating fundamental cellular processes such as cell cycle, immune and inflammation responses, development, differentiation, and transformation. The ubiquitin-proteasome system accounts for the degradation of the majority of cellular short-lived proteins. This system involves the conjugation of multiple ubiquitin residues to the target protein and its recognition by the 26S proteasome through the poly-ubiquitin chain. Studies on the degradation of ornithine decarboxylase (ODC) demonstrated that poly-ubiquitin is not the only signal recognized by the 26S proteasome. The recognition of ODC by the 26S proteasome is mediated by interaction with a polyamine-induced protein termed, antizyme (Az). While the degradation of ODC is ubiquitin-independent, the degradation of its regulator Az, and of antizyme-inhibitor (AzI), an ODC homologous protein that regulates Az availability, are ubiquitin dependent. Interestingly, ODC undergoes another type of ubiquitin-independent degradation by the 20S proteasome that is regulated by NAD(P)H quinone oxidoreductase 1 (NQO1). Considering the prevalence of the ubiquitin system in the process of cellular protein degradation it is rather remarkable that a key cellular enzyme is subjected to two different proteolytic pathways that are different from the ubiquitin dependent one. This exceptional behavior of ODC provides us with valuable insights regarding protein degradation in general.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. chaim.kahana@weizmann.ac.il
authors.forename: Chaim
authors.initials: C
authors.lastname: Kahana
authors.forename: Gad
authors.initials: G
authors.lastname: Asher
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shaul
mesh_terms: D049109:Cell Proliferation; D006868:Hydrolysis; D007424:Intracellular Fluid / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009955:Ornithine Decarboxylase