The unfolded protein response has a protective role in yeast models of classic galactosemia.

Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The ...
synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to cellular adaptation in these models of classic galactosemia.
Mesh Terms:
Alternative Splicing, Basic-Leucine Zipper Transcription Factors, Endoplasmic Reticulum, Fungal Proteins, Galactokinase, Galactose, Galactosemias, Galactosephosphates, Gene Expression Regulation, Fungal, Glycoproteins, HSP70 Heat-Shock Proteins, Humans, Mutation, Oxidoreductases Acting on Sulfur Group Donors, Protein Folding, RNA, Messenger, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Unfolded Protein Response
Dis Model Mech
Date: Jan. 01, 2014
Download Curated Data For This Publication
184575
Switch View:
  • Interactions 3