Giorgini F~Muchowski PJ, 2005

Pubmed ID 15806102
Title A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease.
Authors Flaviano Giorgini, Paolo Guidetti, QuangVu Nguyen, Simone C Bennett, Paul J Muchowski
Abstract Huntington disease is a fatal neurodegenerative disorder caused by expansion of a polyglutamine tract in the protein huntingtin (Htt), which leads to its aggregation in nuclear and cytoplasmic inclusion bodies. We recently identified 52 loss-of-function mutations in yeast genes that enhance the toxicity of a mutant Htt fragment. Here we report the results from a genome-wide loss-of-function suppressor screen in which we identified 28 gene deletions that suppress toxicity of a mutant Htt fragment. The suppressors are known or predicted to have roles in vesicle transport, vacuolar degradation, transcription and prion-like aggregation. Among the most potent suppressors was Bna4 (kynurenine 3-monooxygenase), an enzyme in the kynurenine pathway of tryptophan degradation that has been linked directly to the pathophysiology of Huntington disease in humans by a mechanism that may involve reactive oxygen species. This finding is suggestive of a conserved mechanism of polyglutamine toxicity from yeast to humans and identifies new candidate therapeutic targets for the treatment of Huntington disease.
Citation Nat. Genet. 2005; 37:526-31


Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
Giorgini F~Muchowski PJ, 2005 growth (pooled CFU) expression of mutant huntingtin fragment [GAL] hap a 4,838 Discrete

Curation history

Feb. 25, 2014 Tested strains requested.
Feb. 25, 2014 Data waiting for tested.
Feb. 26, 2014 Tested strains to load.
Feb. 26, 2014 Data to load.
March 3, 2014 Tested strains loaded.
March 3, 2014 Data loaded.