Synthetic genetic circuitry created by researchers at Rice University is helping them see, for the first time, how to regulate cell mechanisms that degrade the misfolded proteins implicated in Parkinson’s, Huntington’s and other diseases. The Rice lab of chemical and biomolecular engineer Laura Segatori has designed a sophisticated circuit that signals increases in the degradation of proteins by the cell’s ubiquitin proteasome system (UPS). The research appears online in Nature Communications. The Deg-On system, an engineered regulator, controls the expression of a fluorescent reporter. Activation of the ubiquitin proteasome system (UPS) enhances degradation of the regulator and leads to an increase in fluorescent output. Tetracycline, an inducer, can be used to fine-tune the system and optimize detection of different levels of UPS activation. Courtesy of the Segatori Group The UPS is essential to a variety of fundamental cellular processes, including the cell cycle, DNA repair, immune response, cell death and the degradation of misfolded and damaged proteins. It has several components: ubiquitin molecules that tag misfolded proteins for degradation and proteasomes that latch onto the tagged proteins and break them down into harmless peptides. When there are too few proteasomes in a cell, or they don’t function properly, misfolded proteins that remain floating in
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