tailieunhanh - Báo cáo khoa học: New roles of flavoproteins in molecular cell biology: An unexpected role for quinone reductases as regulators of proteasomal degradation

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. | ỊFEBS Journal MINIREVIEW New roles of flavoproteins in molecular cell biology An unexpected role for quinone reductases as regulators of proteasomal degradation Sonja Sollner and Peter Macheroux Technische Universitat Graz Institut fur Biochemie Austria Keywords flavin NAD P H ornithine decarboxylase oxidative stress peptide flip proteasome redox state reduction transcription factors ubiquitination Correspondence P. Macheroux Graz University of Technology Institute of Biochemistry Petersgasse 12 II A-8010 Graz Austria Fax 43 316 873 6952 Tel 43 316 873 6450 E-mail Received 9 December 2008 revised 29 April 2009 accepted 4 May 2009 doi 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 proteaso-mal 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 p73a 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