Quinone reductase acts as a redox switch of the 20S yeast proteasome.
The proteasome has an essential function in the intracellular degradation of protein in eukaryotic cells. We found that the dimeric quinone reductase Lot6 uses the flavin mononucleotide (FMN)-binding site to bind to the 20S proteasome with a 1:2 stoichiometry-that is, one 20S proteasome molecule can associate with two quinone reductases. Furthermore, reduction of the FMN cofactor by either NADH or light irradiation results in the binding of the b-Zip transcription factor Yap4 to the Lot6-proteasome complex, indicating that recruitment of the transcription factor depends on the redox state of the quinone reductase. Here, we show that binding of Yap4 to the complex not only protects it from ubiquitin-independent proteasomal degradation, but also regulates its cellular localization. In non-stressed wild-type cells, we did not detect any Yap4 in the nucleus, whereas Yap4 was present in the nuclei from quinone-stressed yeast cultures. Thus, the Lot6-proteasome complex can be regarded as a redox switch in which the quinone reductase acts as a sensor for oxidative stress.
Sollner
Sonja
S
Institute of Biochemistry, Graz University of Technology, Graz, Austria.
Schober
Markus
M
Wagner
Andrea
A
Prem
Anna
A
Lorkova
Lucie
L
Palfey
Bruce A
BA
Groll
Michael
M
Macheroux
Peter
P
D038181:FMN Reductase / Q000235:genetics / Q000378:metabolism*; D005415:Flavins / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C422266:Cin5 protein, S cerevisiae; D005415:Flavins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D038181:FMN Reductase; C490376:LOT6 protein, S cerevisiae; D016660:NAD(P)H Dehydrogenase (Quinone); D046988:Proteasome Endopeptidase Complex