As a consequence of strong recruitment of its mRNA to polysomes, TXNIP protein becomes rapidly and robustly translated under ER stress (Figure 1J and K). Rapid, high-level induction of TXNIP under ER stress is reminiscent of its induction under high ambient glucose (Figure S1, A–C) (Shalev et al., 2002). TXNIP was previously found to be induced by oxidant stress (e.g., H2O2) (Zhou et al., 2010), but we found that it also becomes induced upon exposure to the cell-permeable reductant dithiothreitol (DTT), which reduces disulfide bonds in the ER to cause protein misfolding (Figure S1, D, E). Taken together, these data demonstrate that diverse perturbations in ER protein folding cause robust and rapid induction of the Txnip gene, at both the mRNA and protein level.
