Strategy for Identifying UPR Targets

In the laboratory, the UPR is experimentally induced by the addition of chemical agents known to interfere with protein folding in the ER (Chapman et al., 1998). In yeast, reagents commonly employed are 

1998)]. This average shows a rapid response which is largely but not entirely complete after 15 minutes, steady or slowly increasing over the two-hour DTT time course, and minimal in UPR mutant samples (Fig. 5). 

Genes that passed the primary (correlation) screen for similarity to the known UPR target genes were secondarily screened by a statistical 

The UPR is in many ways nearly ideally suited for the above analysis. The mechanism of the UPR has been studied in detail, and the genes required for pathway activation identified. The response is not essential, and therefore the genes involved can be readily eliminated in yeast, allowing study of knockout strains. Additionally, there are two mechanistically unrelated drugs (DTT and tunicamycin) that cause specific defects in folding in the ER. Without such an impressive arsenal for specifically dissecting the UPR, it would have been possible to delineate some, but not all, of the features of the response. 

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