Nahlik, Krystyna

English

The COP9 signalosome (CSN) is a conserved eukaryotic            multiprotein complex, playing a multifaceted role in            the regulation of protein degradation by the ubiquitin            system. The primary function of CSN is the removal of            the ubiquitin-like Nedd8 moiety from the cullin            subunits of SCF ubiquitin ligases, termed            deneddylation. A complete conserved CSN was previously            isolated in the model filamentous fungus Aspergillus            nidulans, where it is necessary for sexual fruit            body formation and establishment of developmental            balance, but not essential for survival, providing an            opportunity to study the functions of this complex in a            genetically amenable organism.In the course of this work I have investigated the            mechanism of CSN action during A. nidulans            development using two complementary approaches:            mutagenic analysis of the deneddylase-bearing CsnE            subunit and transcriptome profiling of a csnE deletion            strain.Mutagenesis of the JAMM metalloprotease motif            reveals that it is primarily responsible for the csn            deletion phenotype and therefore the deneddylase            activity is probably essential for A. nidulans            sexual development. Mutated CsnE is still able to            interact with CsnF, another CSN subunit, indicating            that the phenotype is not caused by impaired complex            formation. We additionally show that rubA, a close            homologue of mammalian Nedd8 is essential for A.            nidulans growth.The results of the genome-wide transcriptome            profiling of a csnE deletion strain show that the            fungal CSN affects the regulation of many groups of            genes across development. Differentially expressed            genes include oxidoreductases, genes involved in cell            wall degradation and membrane transport as well as a            putative cluster of secondary metabolite biosynthesis            genes. CSN is required for developmentally induced            expression of brlA, the central regulator of asexual            sporulation and the hormone synthesis oxygenase ppoC            involved in regulation of developmental balance. It is            also necessary for developmentally induced            beta-glucanase activity, which might be prerequisite            for fruit body formation. Analysis of cis-regulating            sequences upstream of regulated genes suggests a            possibility of crosstalk between the sexual and asexual            signalling pathways. The results obtained in this work            provide a basis for further elucidating transcriptional            networks acting in A. nidulans developmental            signalling and afford for insights into downstream            targets of CSN in eukaryotes.The COP9 signalosome (CSN) is a conserved eukaryotic            multiprotein complex, playing a multifaceted role in            the regulation of protein degradation by the ubiquitin            system. The primary function of CSN is the removal of            the ubiquitin-like Nedd8 moiety from the cullin            subunits of SCF ubiquitin ligases, termed            deneddylation. A complete conserved CSN was previously            isolated in the model filamentous fungus Aspergillus            nidulans, where it is necessary for sexual fruit            body formation and establishment of developmental            balance, but not essential for survival, providing an            opportunity to study the functions of this complex in a            genetically amenable organism.In the course of this work I have investigated the            mechanism of CSN action during A. nidulans            development using two complementary approaches:            mutagenic analysis of the deneddylase-bearing CsnE            subunit and transcriptome profiling of a csnE deletion            strain.Mutagenesis of the JAMM metalloprotease motif            reveals that it is primarily responsible for the csn            deletion phenotype and therefore the deneddylase            activity is probably essential for A. nidulans            sexual development. Mutated CsnE is still able to            interact with CsnF, another CSN subunit, indicating            that the phenotype is not caused by impaired complex            formation. We additionally show that rubA, a close            homologue of mammalian Nedd8 is essential for A.            nidulans growth.The results of the genome-wide transcriptome            profiling of a csnE deletion strain show that the            fungal CSN affects the regulation of many groups of            genes across development. Differentially expressed            genes include oxidoreductases, genes involved in cell            wall degradation and membrane transport as well as a            putative cluster of secondary metabolite biosynthesis            genes. CSN is required for developmentally induced            expression of brlA, the central regulator of asexual            sporulation and the hormone synthesis oxygenase ppoC            involved in regulation of developmental balance. It is            also necessary for developmentally induced            beta-glucanase activity, which might be prerequisite            for fruit body formation. Analysis of cis-regulating            sequences upstream of regulated genes suggests a            possibility of crosstalk between the sexual and asexual            signalling pathways. The results obtained in this work            provide a basis for further elucidating transcriptional            networks acting in A. nidulans developmental            signalling and afford for insights into downstream            targets of CSN in eukaryotes

Georg-August-University Göttingen

Regulation of protein degradation and transcriptional pathways in sexual development

https://ediss.uni-goettingen.de/bitstream/11858/00-1735-0000-0006-B4EA-B/1/nahlik.pdf

Regulation of protein degradation and transcriptional pathways in sexual development

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Georg-August-University Göttingen