The role of Yca1 in Proteostasis. Yca1 Regulates the Composition of the Insoluble Proteome.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Journal of proteomics (Impact Factor: 3.89). 01/2013; 81. DOI: 10.1016/j.jprot.2013.01.014
Source: PubMed


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 S. 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.

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Available from: Amit Shrestha, Jan 12, 2016
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    • "On the other hand, the ability of metacaspase to both promote and antagonize different cell cycle checkpoints has been demonstrated, representing an early form of the proliferation/ differentiation regulatory activity exhibited by metazoan caspases [16]. YCA1 also contributes to the fitness and adaptability of growing yeast through clearance of insoluble protein aggregates [17] [18] and has been implicated in the regulation of antioxidant status and mitochondrial respiration [15] [19] [20]. The concept of non-apoptotic roles of metacaspase has been expanded in our previous work in which we have performed a comparative analysis between wild type and Δyca1 cells using combined proteomic and metabolomic approach. "
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