Document Detail

Repression of N-glycosylation triggers the unfolded protein response (UPR) and over-expression of cell wall protein and chitin in Aspergillus fumigatus.
MedLine Citation:
PMID:  21527474     Owner:  NLM     Status:  Publisher    
Aspergillus fumigatus is the most common airborne fungal pathogen, causing fatal invasive aspergillosis in immunocompromised patients. The crude mortality is 60-90% and remains around 29-42% even treated. The main reason for patient death is the low efficiency of the drug therapies. As protein N-glycosylation is involved in cell wall biogenesis in A. fumigatus, a deep understanding of its role in cell wall biogenesis will help to develop new drug targets. The Afstt3 gene encodes the essential catalytic subunit of oligosaccharyltransferase, an enzyme complex responsible for transfer of the N-glycan to nascent polypeptides. To evaluate the role of N-glycosylation in cell wall biosynthesis, we constructed the conditional mutant strain CPR-stt3 by replacing the endogenous promoter of Afstt3 with the nitrogen-dependent niiA promoter. Repression of the Afstt3 gene in the CPR-stt3 strain led to a severe retardation of growth and a slight defect in cell wall integrity. One of the most interesting findings was that up-regulation of the cell wall-related genes was not accompanied by an activation of the MpkA kinase, which has been shown as a central element in the cell wall integrity (CWI) signaling pathway in both S. cerevisiae and A. fumigatus. Considering that the unfolded protein response (UPR) was found to be activated, which might up-regulate the expression of cell wall protein and chitin, our data suggest that UPR, instead of the MpkA-dependent CWI signaling pathway, is the major compensatory mechanism induced by repression but not abolition of N-glycosylation in A. fumigatus. Our finding is a key to understanding complex compensatory mechanisms of cell wall biosynthesis and may provide a new strategy for drug development.
Kai Li; Haomiao Ouyang; Yang Lü; Jingnan Liang; Iain B H Wilson; Cheng Jin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-28
Journal Detail:
Title:  Microbiology (Reading, England)     Volume:  -     ISSN:  1465-2080     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9430468     Medline TA:  Microbiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Microbiology, Chinese Academy of Sciences;
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