The role of Yca1 in proteostasis. Yca1 regulates the composition of the insoluble proteome

J Proteomics. 2013 Apr 9;81:24-30. doi: 10.1016/j.jprot.2013.01.014. Epub 2013 Jan 30.

Abstract

Proteostasis, the process of balancing protein production with protein degradation is vital to normal cell function. Defects within the mechanisms that control proteostasis lead to increased content of a specialized insoluble protein fraction that forms dense aggregates within the cell. We have previously implicated the Saccharomyces cerevisiae metacaspase Yca1 as an active participant in maintaining proteostasis, whereby Yca1 acts to limit aggregate content. Here, we further characterized the proteostasis role of Yca1 by conducting proteomic analysis of the insoluble protein fraction in wildtype and Yca1 knockout cells, under normal and heat stressed conditions. Our findings suggest that the composition of insoluble protein fraction is non-specific and comprises a wide array of protein species rather than a limited repertoire of aggregate susceptible proteins or peptides. Interestingly, the loss of Yca1 led to a significant decrease of proteins that control ribosome biogenesis and protein synthesis within the insoluble fraction, indicating that the cell may invoke a compensatory mechanism to limit protein production during stress, a feature dependent on Yca1 activity. Finally, we noted that protein degradation factors such as Cdc48 co-localize with Yca1 to the insoluble fraction, supporting the hypothesis that Yca1 may act primarily to dissolve or reduce accumulated aggregates. This article is part of a Special Issue entitled: From protein structures to clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Caspases / genetics
  • Caspases / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Gene Knockdown Techniques
  • Protein Biosynthesis / physiology
  • Protein Transport / physiology
  • Proteolysis
  • Proteome / genetics
  • Proteome / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Solubility
  • Stress, Physiological / physiology
  • Valosin Containing Protein

Substances

  • Cell Cycle Proteins
  • Proteome
  • Saccharomyces cerevisiae Proteins
  • Caspases
  • MCA1 protein, S cerevisiae
  • Adenosine Triphosphatases
  • CDC48 protein, S cerevisiae
  • Valosin Containing Protein