title: New roles of flavoproteins in molecular cell biology: an unexpected role for quinone reductases as regulators of proteasomal degradation.
abstract: Quinone reductases are ubiquitous soluble enzymes found in bacteria, fungi, plants and animals. These enzymes utilize a reduced nicotinamide such as NADH or NADPH to reduce the flavin cofactor (either FMN or FAD), which then affords two-electron reduction of cellular quinones. Although the chemical nature of the quinone substrate is still a matter of debate, the reaction appears to play a pivotal role in quinone detoxification by preventing the generation of potentially harmful semiquinones. In recent years, an additional role of quinone reductases as regulators of proteasomal degradation of transcription factors and possibly intrinsically unstructured protein has emerged. To fulfil this role, quinone reductase binds to the core particle of the proteasome and recruits certain transcription factors such as p53 and p73alpha to the complex. The latter process appears to be governed by the redox state of the flavin cofactor of the quinone reductase, thus linking the stability of transcription factors to cellular events such as oxidative stress. Here, we review the current evidence for protein complex formation between quinone reductase and the 20S proteasome in eukaryotic cells and describe the regulatory role of this complex in stabilizing transcription factors by acting as inhibitors of their proteasomal degradation.
authors.affiliation: Technische Universität Graz, Institut für Biochemie, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sollner
authors.forename: Peter
authors.initials: P
authors.lastname: Macheroux
mesh_terms: D005420:Flavoproteins / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D011808:Quinone Reductases / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D005420:Flavoproteins; D014157:Transcription Factors; D011808:Quinone Reductases; D046988:Proteasome Endopeptidase Complex