XBP-1 is a transcription factor that plays a critical role in the unfolded protein response (UPR) and is involved in the regulation of ER proteome maintenance. Its function is essential for the secretory function of cells, particularly in the capacity of the endoplasmic reticulum (ER) to fold and modify nascent polypeptides and to synthesize phospholipids for the subsequent trafficking of secretory proteins through the ER–Golgi network1.
- Regulation of ER Proteome Maintenance: XBP-1 is involved in the maintenance of the ER proteome, which declines with age2. This decline in ability to activate protective stress responses early in adulthood may contribute to age-related diseases.
- Secretory Function of Cells: XBP-1 is required for the full biogenesis of the secretory machinery in exocrine cells. Its absence leads to an imbalance between the cargo load on the ER and its capacity to handle it, resulting in the activation of ER stress-mediated proapoptotic pathways1.
- Non-Coding RNA Function: An RNA fragment produced from XBP-1 mRNA, known as xbp-1 ncRNA, is essential for axon regeneration in Caenorhabditis elegans. This ncRNA acts independently of the protein-coding function of the XBP-1 transcript, part of a dual output xbp-1 mRNA stress response axis3.
In summary, XBP-1 is a critical regulator of ER proteome maintenance and secretory function of cells, its dysfunction can lead to ER stress and impaired secretory function, contributing to various diseases.
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