Proteomics

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Candida albicans is resistant to polyglutamine aggregation and toxicity


ABSTRACT: Disruption of protein quality control can be detrimental, having toxic effects on single cell organisms, and causing neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s in humans. Here we examined the effects of polyQ aggregation in a major fungal pathogen of humans, Candida albicans, with the goal of identifying new approaches to disable this fungus. However, we discovered that expression of poly-glutamine (polyQ) stretches up to 230Q had no effect on C. albicans ability to grow and withstand proteotoxic stress. Bioinformatics analysis demonstrates that C. albicans has a similarly glutamine rich proteome to the unicellular fungus Saccharomyces cerevisiae, which exhibits polyQ toxicity with as few as 72Q. Surprisingly, global transcriptional profiles indicated no significant change upon induction of up to 230Q. Proteomic analysis highlighted two key interactors of 230Q, Sis1 and Sgt2, however, loss of either protein had no additional effect on C. albicans toxicity. Our data suggest that C. albicans has evolved powerful mechanisms to overcome aggregation prone proteins, providing a unique model for studying polyQ associated diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Candida Albicans (yeast)

SUBMITTER: Jonathan Krieger  

LAB HEAD: Leah E. Cowen

PROVIDER: PXD003916 | Pride | 2016-12-05

REPOSITORIES: Pride

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Publications

Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity.

Leach Michelle D MD   Kim TaeHyung T   DiGregorio Sonja E SE   Collins Cathy C   Zhang Zhaolei Z   Duennwald Martin L ML   Cowen Leah E LE  

G3 (Bethesda, Md.) 20170105 1


Disruption of protein quality control can be detrimental, having toxic effects on single cell organisms and contributing to neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's in humans. Here, we examined the effects of polyglutamine (polyQ) aggregation in a major fungal pathogen of humans, Candida albicans, with the goal of identifying new approaches to disable this fungus. However, we discovered that expression of polyQ stretches up to 230Q had no effect on C. albicans  ...[more]

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