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Chunk #7 — RESULTS — Thioredoxin-interacting protein (TXNIP) is rapidly induced through the UPR

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IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress.
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Of other significantly induced genes on the list, we focused our attention on thioredoxin-interacting protein, TXNIP. TXNIP was first described as a binding partner of thioredoxin that regulates its antioxidant functions (Nishiyama et al., 1999; Patwari et al., 2006; Yamanaka et al., 2000). As TXNIP had been implicated in glucotoxicity-induced apoptosis of β-cells (Chen et al., 2008; Shalev, 2008), we reasoned that it may also mediate programmed cell death in response to ER stress; therefore we embarked on experiments to investigate the underlying mechanisms and physiology of this putative link.