Date: 09 Dec 2010

Effects of Protein Quality Control Machinery on Protein Homeostasis

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In the endoplasmic reticulum, protein production occurs through a complex set of reaction networks which synthesize and fold protein polypeptides. Proteins can misfold due to mutation or cellular stress. Accumulation of misfolded proteins can lead to the formation of toxic protein aggregates. Cells have evolved the unfolded protein response which removes misfolded proteins from the endoplasmic reticulum before aggregation can occur. Failure of protein synthesis and folding quality control is associated with disease. We are beginning to comprehend how these processes are controlled. Here, we develop two mathematical models to investigate how cellular quality control regulates protein homeostasis. Using parametric sensitivity analysis, we identify pathway parameters involved in increasing folded protein production.