Figure 2

Effect of IRE1 inhibition on global changes in mRNA expression in response to mutant proinsulin production. Insulin 2 C96Y-GFP cells were treated with 2 μg/ml doxycycline for 48 h to induce expression of the insulin 2(C96Y)-GFP fusion protein in the presence or absence of 5 μM 4μ8c. Total RNA was isolated from cells and hybridized to Affymetrix microarray chips. Log2 normalized mRNA fold change values relative to untreated cells were plotted. Regions of the plot where gene expression has changed greater than 1.5 fold has been expanded and labeled with selected gene names. Gene expression changes >1.5 fold resulting from doxycycline-induced expression of mutant proinsulin (top and right boxes). Genes no longer induced >1.5 fold in the presence of 4u8c are indicated in red (right box), while those still induced >1.5 fold in the presence of 4u8c are indicated in green (top box). Genes reduced >1.5 fold resulting from doxycycline-induced expression of mutant proinsulin (left and bottom boxes). Genes no longer reduced >1.5 fold in the presence of 4u8c are indicated in red (left box), while those still reduced >1.5 fold in the presence of 4u8c are indicated in green (bottom box). Results are from N=2 independent experiments.