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

Fingerprint

unfolded protein response
fungi
proteins
Trichoderma reesei
phosphotransferases (kinases)
yeasts
Aspergillus niger
genes
introns
transcription factors
promoter regions
protein disulfide-isomerase
chymosin
Coriolus versicolor
Aspergillus nidulans
protein secretion
reticulum
dephosphorylation
laccase
beta-fructofuranosidase

Cite this

Saloheimo, M., Valkonen, M., Ward, M., & Penttilä, M. (2002). The unfolded protein response pathway in filamentous fungi. In G. Palamarczyk (Ed.), European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi (pp. 17)
Saloheimo, Markku ; Valkonen, Mari ; Ward, Michael ; Penttilä, Merja. / The unfolded protein response pathway in filamentous fungi. European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi. editor / Grażyna Palamarczyk. 2002. pp. 17
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Saloheimo, M, Valkonen, M, Ward, M & Penttilä, M 2002, The unfolded protein response pathway in filamentous fungi. in G Palamarczyk (ed.), European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi. pp. 17, European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi, Wierzba, Poland, 15/09/02.

The unfolded protein response pathway in filamentous fungi. / Saloheimo, Markku (Corresponding author); Valkonen, Mari; Ward, Michael; Penttilä, Merja.

European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi. ed. / Grażyna Palamarczyk. 2002. p. 17.

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

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T1 - The unfolded protein response pathway in filamentous fungi

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AU - Valkonen, Mari

AU - Ward, Michael

AU - Penttilä, Merja

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PY - 2002

Y1 - 2002

N2 - Proteins destined to be secreted from eukaryotic cells are translocated to theendoplasmic 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 ERmembrane 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 ofIre1p 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 proteinphosphatase 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.

AB - Proteins destined to be secreted from eukaryotic cells are translocated to theendoplasmic 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 ERmembrane 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 ofIre1p 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 proteinphosphatase 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.

M3 - Conference abstract in proceedings

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BT - European Commission, 5th Framework Programme

A2 - Palamarczyk, Grażyna

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Saloheimo M, Valkonen M, Ward M, Penttilä M. The unfolded protein response pathway in filamentous fungi. In Palamarczyk G, editor, European Commission, 5th Framework Programme: Centre of Excellence in Molecular Biotechnology Meeting Protein Secretion and Glycosylation in Yeast and Filamentous Fungi. 2002. p. 17