Integration of unfolded protein response (UPR) to gastrointestinal disease and endoplasmic reticulum (ER) proteostasis targeting. (IMAGE)

First Hospital of Jilin University

Integration of unfolded protein response (UPR) to gastrointestinal disease and endoplasmic reticulum (ER) proteostasis targeting.

Caption

Intestinal epithelial cells (IECs) are exposed to a challenging microenvironment that imposes high pressure on the proteostasis network. Through physiological UPR activation, IECs restore their proteostasis to sustain their function and maintain intestinal homeostasis. However, chronic ER stress triggers non-adaptive UPR signalling that impairs proteostasis recovery. Genetic manipulation of UPR elements has pinpointed their relevance to IEC function and ER stress sensitivity. Overall, UPR abrogation and proteostasis impairment induce cellular and tissue dysfunction, favouring bacterial infection and a proinflammatory state that increases susceptibility to colitis and tumorigenesis. Interventions with small molecules to improve ER proteostasis under specific pathological models are also highlighted. ATF6, activating transcription factor-6; IRE1, inositol-requiring enzyme 1; 4-PBA, 4-phenylbutyrate; PERK, protein kinase RNA-like ER kinase; TUDCA, tauroursodeoxycholate; XBP1, X-Box-binding protein 1.

Credit

By Claudio Hetz, Juan Francisco Silva-Agüero, Lisa M Ellerby

Usage Restrictions

Credit must be given to the creator. Only noncommercial uses of the work are permitted.

License

CC BY-NC

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