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

Tafforeau, Lionel; Blastier, Sophie Le; Bamps, Sophie; Dewez, Monique; Vandenhaute, Jean; Hermand, Damien

doi:10.1038/sj.emboj.7601329

Cited by 30 publications

(25 citation statements)

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“…It has been demonstrated that the deletion of single genes in the ergosterol synthesis pathway rendered yeast cells more susceptible to oxidative stress (Branco et al 2004; Thorpe et al 2004). In addition, H2O2 was found to repress the ergosterol biosynthesis pathway through Pof14, a new member of the Fbox protein family, which binds and decreases the activity of the squalene synthase ERG9, a key enzyme in ergosterol metabolism, leading to a decrease of the total cellular ergosterol levels in Schizosaccharomyces pombe (Tafforeau et al 2006). Modulation of sterol level plays, therefore, a key role in adaptation to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a CuZn superoxide dismutase gene in the arbuscular mycorrhizal fungus Glomus intraradices

et al. 2010

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To gain further insights into the mechanisms of redox homeostasis in arbuscular mycorrhizal fungi, we characterized a Glomus intraradices gene (GintSOD1) showing high similarity to previously described genes encoding CuZn superoxide dismutases (SODs). The GintSOD1 gene consists of an open reading frame of 471 bp, predicted to encode a protein of 157 amino acids with an estimated molecular mass of 16.3 kDa. Functional complementation assays in a CuZnSOD-defective yeast mutant showed that GintSOD1 protects the yeast cells from oxygen toxicity and that it, therefore, encodes a protein that scavenges reactive oxygen species (ROS). GintSOD1 transcripts differentially accumulate during the fungal life cycle, reaching the highest expression levels in the intraradical mycelium. GintSOD1 expression is induced by the well known ROS-inducing agents paraquat and copper, and also by fenpropimorph, a sterol biosynthesis inhibitor (SBI) fungicide. These results suggest that GintSOD1 is involved in the detoxification of ROS generated from metabolic processes and by external agents. In particular, our data indicate that the antifungal effects of fenpropimorph might not be only due to the interference with sterol metabolism but also to the perturbation of other biological processes and that ROS production and scavenging systems are involved in the response to SBI fungicides.

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Section: Discussionmentioning

confidence: 99%

Characterization of a CuZn superoxide dismutase gene in the arbuscular mycorrhizal fungus Glomus intraradices

et al. 2010

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“…However, binding of Pof14 to Skp1 may promote the degradation of Pof14 itself. In wild-type cells, Pof14 has a half-life of 20 to 40 min, but in temperature-sensitive mutants of Skp1, Pof14 is stable for at least 60 min (193). Whether this stabilization is due to defective assembly of Skp1 and Pof14 into an SCF complex for self-ubiquitination is not known.…”

Section: Pof14: An F-box Protein That Inhibits Ergosterol Synthesismentioning

confidence: 97%

“…Transcription of POF14 is induced after treatment with hydrogen peroxide, and deletion of POF14 decreases viability after hydrogen peroxide treatment (193). Decreased viability was not observed upon deletion of the F-box domain, suggesting that binding of Pof14 to Skp1 is not required for peroxide resistance.…”

Section: Pof14: An F-box Protein That Inhibits Ergosterol Synthesismentioning

confidence: 98%

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Lessons from Fungal F-Box Proteins

Jonkers

Rep

2009

Eukaryot Cell

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“…Immunoprecipitations were performed as described previously (20). In short, cells were disrupted with a Fastprep (MP Biochemical), and proteins were precipitated on appropriately coated Dynabeads (Invitrogen) following the instructions of the manufacturer (38). Cdc2 was precipitated using p13-Suc1 beads (Upstate Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

Fission Yeast Cdk7 Controls Gene Expression through both Its CAK and C-Terminal Domain Kinase Activities

DEVOS

Mommaerts

Migeot

et al. 2015

Molecular and Cellular Biology

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Cyclin-dependent kinases (Cdk) coordinate timely progression through the cell cycle. Cdk activity is modulated by the association of regulatory subunits (cyclins, inhibitors, and assembly factors) and by activating and inhibiting phosphorylation at conserved residues (1). Phosphorylation within the activating segment, referred to as the T loop, is essential for maximal activity and is catalyzed by a Cdk-activating kinase (CAK) (2, 3). Genetic and biochemical studies in several model organisms pointed to Cdk7-cyclin H-Mat1 as the in vivo CAK in metazoans. Cdk7 specifically phosphorylates both Cdk1 and Cdk2 in human cells (4-6), and elegant experiments using chemical genetics showed that Cdk7 is required for the assembly of Cdk1-cyclin B (7). CAK activity is decreased in cdk7 mutants in either Drosophila (8) or worms (9). However, correlations between biochemical data and phenotypes have always been complicated by the additional role of Cdk7 in transcription (10). Indeed, the trimeric CAK is also a component of the RNA polymerase II (Pol II) general transcription factor TFIIH, where it phosphorylates the C-terminal domain (CTD) of Rpb1, the largest subunit of the Pol II enzyme (11,12). Within the Cdk family, Cdk7 also is distinct in being activated by either a phosphorylation on its T loop or by the assembly factor Mat1 (13). These functions and regulations of Cdk7 are conserved in the budding yeast Saccharomyces cerevisiae, where its ortholog, Kin28, is well described as a CTD kinase regulating transcription (14, 15). Intriguingly, Kin28 is devoid of CAK activity (16), and Cak1, a divergent, single-subunit kinase distantly related to Cdk (17, 18), instead catalyzes Cdk activation at both transitions of the budding yeast cell cycle.The fission yeast Schizosaccharomyces pombe possesses two CAKs, the nonessential Csk1 and the essential Mcs6 kinases, corresponding to the yeast Cak1 and the metazoan Cdk7, respectively (19-25). Csk1 activates Mcs6 by phosphorylation of the T loop on serine 165 (20), and a widely held view is that the two CAKs act redundantly for Cdc2 activation (22,24), implying that inactivation of Mcs6 reveals the sole role of Cdk7 in transcription. However, strong genetic data argue against the idea that Csk1 contributes significantly to Cdc2 activation in vivo. First, the original mutant alleles of both the mcs6 (mcs6-13) and mcs2 (mcs2-75) genes, which, respectively, encode Cdk7 and cyclin H, were independently identified in a screen for suppressor of mitotic catastrophe, a phenotype resulting from hyperactive Cdc2, and both show allele-specific interaction with cdc2 (23). This is inconsistent with a functional redundancy with Csk1, as the strain was otherwise wild type for csk1. Moreover, another allele of fission yeast cdk7 (mcs6 S165A L238R [the S-to-A change at position 165 and the L-to-R change at position 238 encoded by mcs6]) leads to thermosensitivity associated with decreased Cdc2 phosphorylation (24), and the growth defect is suppressed by Cdc2 activators or by budding yeast Cak1 but not...

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

Cited by 30 publications

References 54 publications

Characterization of a CuZn superoxide dismutase gene in the arbuscular mycorrhizal fungus Glomus intraradices

Characterization of a CuZn superoxide dismutase gene in the arbuscular mycorrhizal fungus Glomus intraradices

Lessons from Fungal F-Box Proteins

Fission Yeast Cdk7 Controls Gene Expression through both Its CAK and C-Terminal Domain Kinase Activities

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