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Chunk #30 — DISCUSSION — TXNIP is a signaling hub through which cells respond to irremediable ER stress

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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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TXNIP mRNA stability during ER stress is under control of a specific micro-RNA, miR-17. miRs control gene expression at post-transcriptional levels by destabilizing target mRNAs and/or by repressing translation. Highly conserved seed sequences for miR-17 in the TXNIP 3′-UTR were found to govern post-transcriptional regulation of TXNIP mRNA under ER stress. Furthermore, steady-states levels of TXNIP mRNA could be predictably modulated: either down with a miR-17 mimic, or up with anti-miR-17. Forcible activation of IRE1α is sufficient to decrease cellular miR-17 levels, and endogenous IRE1α is necessary to decrease miR-17 under irremediable ER stress.