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  • The EMBO Journal (2006) 25, 4547 - 4556
  • doi:10.1038/sj.emboj.7601329

Published online: 14 September 2006

Repression of ergosterol level during oxidative stress by fission yeast F-box protein Pof14 independently of SCF

Lionel Tafforeau, Sophie Le Blastiera, Sophie Bampsa, Monique Dewez, Jean Vandenhaute and Damien Hermand

  1. Laboratoire de Génétique Moléculaire (GEMO), Unité de Recherche en Biologie Moléculaire (URBM), Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium

Correspondence to:

Damien Hermand, Laboratoire de Genetique Moleculaire, University of Namur, Facultes Universitaires Notre Dame de la Paix, 61 Rue de Bruxelles, B-5000 Namur, Belgium. Tel.: +32 81 724241; Fax: +32 81 724297; E-mail: damien.hermand@fundp.ac.be

aThese authors contributed equally to this work

Received 21 February 2006; Accepted 14 August 2006

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.

  • Keywords:

    • Erg9,
    • fission yeast,
    • hydrogen peroxide,
    • sterol