Repression of ergosterol level during oxidative stress by fission yeast F-box protein Pof14 independently of SCF.
We describe a new member of the F-box family, Pof14, which forms a canonical, F-box dependent SCF (Skp1, Cullin, F-box protein) ubiquitin ligase complex. The Pof14 protein has intrinsic instability that is abolished by inactivation of its Skp1 interaction motif (the F-box), Skp1 or the proteasome, indicating that Pof14 stability is controlled by an autocatalytic mechanism. Pof14 interacts with the squalene synthase Erg9, a key enzyme in ergosterol metabolism, in a membrane-bound complex that does not contain the core SCF components. pof14 transcription is induced by hydrogen peroxide and requires the Pap1 transcription factor and the Sty1 MAP kinase. Pof14 binds to and decreases Erg9 activity in vitro and a pof14 deletion strain quickly loses viability in the presence of hydrogen peroxide due to its inability to repress ergosterol synthesis. A pof14 mutant lacking the F-box and an skp1-3 ts mutant behave as wild type in the presence of oxidant showing that Pof14 function is independent of SCF. This indicates that modulation of ergosterol level plays a key role in adaptation to oxidative stress.
Tafforeau
Lionel
L
Laboratoire de Génétique Moléculaire, GEMO, Unité de Recherche en Biologie Moléculaire, URBM, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Le Blastier
Sophie
S
Bamps
Sophie
S
Dewez
Monique
M
Vandenhaute
Jean
J
Hermand
Damien
D
D000222:Adaptation, Physiological; D002384:Catalysis; D003593:Cytoplasm / Q000201:enzymology; D004875:Ergosterol / Q000096:biosynthesis / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology*; D000073718:Pancreatitis-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
D044783:F-Box Proteins; D000073718:Pancreatitis-Associated Proteins; C514730:Pof14 protein, S pombe; C000612141:REG3A protein, human; D029702:Schizosaccharomyces pombe Proteins; D006861:Hydrogen Peroxide; D044843:SKP Cullin F-Box Protein Ligases; D013186:Farnesyl-Diphosphate Farnesyltransferase; D004875:Ergosterol