Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is a very labile protein. ODC is a homodimeric enzyme that undergoes ubiquitin-independent proteasomal degradation via direct interaction with antizyme, a polyamine-induced protein. Binding of antizyme promotes the dissociation of ODC homodimers and marks ODC for degradation by the 26S proteasomes. We describe here an alternative pathway for ODC degradation that is regulated by NAD(P)H quinone oxidoreductase 1 (NQO1). We show that NQO1 binds and stabilizes ODC. Dicoumarol, an inhibitor of NQO1, dissociates ODC-NQO1 interaction and enhances ubiquitin-independent ODC proteasomal degradation. We further show that dicoumarol sensitizes ODC monomers to proteasomal degradation in an antizyme-independent manner. This process of NQO1-regulated ODC degradation was recapitulated in vitro by using purified 20S proteasomes. Finally, we show that the regulation of ODC stability by NQO1 is especially prominent under oxidative stress. Our findings assign to NQO1 a role in regulating ubiquitin-independent degradation of ODC by the 20S proteasomes.
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PMID:20S proteasomal degradation of ornithine decarboxylase is regulated by NQO1. 1574 15

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.
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PMID:Mechanisms of protein degradation: an odyssey with ODC. 1620 22