positive regulation of IRE1-mediated unfolded protein response

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the IRE1-mediated unfolded protein response. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:22013210]

The unfolded protein response (UPR) is a cellular stress response that is activated in response to the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). One of the major branches of the UPR is mediated by the transmembrane protein IRE1α. IRE1α is a type I transmembrane protein with both a cytosolic kinase domain and an endoribonuclease domain. Upon ER stress, IRE1α oligomerizes and activates its endoribonuclease activity, leading to the splicing of the mRNA encoding the transcription factor XBP1. The spliced form of XBP1, XBP1s, acts as a transcription factor that promotes the expression of genes involved in protein folding, ER-associated degradation (ERAD), and other stress response pathways. IRE1α can also activate the downstream signaling pathway by binding to TRAF2 and activating the JNK and NF-κB pathways.
Positive regulation of IRE1-mediated UPR refers to any process that enhances or promotes the activity of IRE1α and its downstream signaling pathways. This can include:
1. Increased expression of IRE1α: Up-regulation of IRE1α expression can be achieved through various mechanisms, including transcriptional activation by stress-responsive transcription factors or post-transcriptional modifications like phosphorylation.
2. Enhanced IRE1α oligomerization: IRE1α oligomerization is essential for its activation. Factors that promote IRE1α oligomerization, such as increased ER stress or specific protein interactions, can positively regulate the UPR.
3. Activation of IRE1α endoribonuclease activity: Factors that increase the catalytic activity of the IRE1α endoribonuclease, such as specific post-translational modifications or protein interactions, can enhance the UPR.
4. Enhanced XBP1 splicing: Increased XBP1 splicing activity can be achieved by factors that promote IRE1α activity or by factors that directly regulate XBP1 splicing.
5. Increased XBP1s translation and stability: Factors that enhance XBP1s translation or protein stability can further promote the UPR.
6. Activation of downstream signaling pathways: Factors that enhance the activity of the JNK and NF-κB pathways downstream of IRE1α can contribute to positive regulation of the UPR.
Overall, positive regulation of IRE1-mediated UPR plays a crucial role in ensuring proper protein folding, ER homeostasis, and cell survival under stress conditions.'
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Proteins (5)

Compounds (239)