Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

Abstract

Accumulation of unfolded proteins within the lumen of the ER results in secretion stress in eukaryotic organisms. The industrial important filamentous fungus Aspergillus niger, responds to this stress by activating a transcriptional activator. This transcriptional activator, HacA, up- regulates its target genes by binding to UPR elements present in the promoters of those genes. These target genes include foldases and chaperones that assist protein folding in the ER. The thesis describes regulation of the A. niger UPR and activation of HacA, which involves a high degree of auto-regulation.