The unfolded protein response pathway in filamentous fungi

Markku Saloheimo (Corresponding author), Mari Valkonen, Michael Ward, Merja Penttilä

    Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsScientific

    Abstract

    Proteins destined to be secreted from eukaryotic cells are translocated to the
    endoplasmic reticulum (ER) where they fold to their active conformation and get coreglycosylated. Numerous ER-resident proteins assist in these events. The genes encoding chaperone proteins like Bip and foldase proteins like protein disulphide isomerase (PDI) and numerous other genes encoding involved in protein secretion are under the control of the unfolded protein response (UPR) pathway, i.e. they are induced when unfolded proteins accumulate into the ER. Several components of the UPR pathway have been characterised from the yeast S. cerevisiae. The transmembrane kinase/RNase Ire1p residing in the ER
    membrane senses the ER lumen for unfolded proteins with its N- terminal domain, and activates the pathway with its C-terminal kinase and RNase domains. The transcription factor acting on the promoters of target genes is Hac1p. The HAC1 gene is activated through a special mRNA splicing event, where Ire1p cleaves the HAC1 mRNA at the borders odf an unconventional intron, and the exons are ligated together by tRNA ligase. The activity of
    Ire1p is modulated by dephosphorylation by the protein phosphatase Ptc2p.
    We have studied the UPR pathway of the filamentous fungi Trichoderma reesei,
    Aspergillus nidulans and Aspergillus niger. The equivalents of the yeast Hac1 transcription factor have been cloned from all three fungi. Our results indicate that the HAC1 genes of filamentous fungi are induced by a dual mechanism operational at the mRNA level. This mechanism includes a splicing event of an unconventional intron of only 20 nt in length and a truncation of the mRNA at the 5' flanking region. This truncation removes an upstream open reading frame from the mRNA, implying translational control of the HAC1 protein formation. The equivalents of the S. cerevisiae kinase/RNAse Ire1p and the protein
    phosphatase Ptc2p have also been cloned from T. reesei and their functions are being elucidated. We have studied the effects of constitutive induction of the UPR pathway on production of native and foreign proteins in S. cerevisiae and A. niger var. awamori. This induction was achieved by expressing the induced form of the HAC1 mRNA from a constitutive promoter. The production of both the native invertase and Bacillus α-amylase was enhanced in the yeast strains with constitutive UPR. Improved production of calf chymosin and Trametes versicolor laccase was obtained in the engineered Aspergiullus niger var awamori strains.
    Original languageEnglish
    Title of host publicationEuropean Commission, 5th Framework Programme
    Subtitle of host publicationCentre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi
    EditorsGrażyna Palamarczyk
    Pages17
    Publication statusPublished - 2002
    EventEuropean Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi - Wierzba, Poland
    Duration: 15 Sep 200218 Sep 2002

    Conference

    ConferenceEuropean Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi
    CountryPoland
    CityWierzba
    Period15/09/0218/09/02

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