Photo by boxedwater from unsplash
Significance Unfolded protein response (UPR) is thought to coordinate cell growth and proliferation by governing endoplasmic reticulum (ER) proteostasis; however, the mechanisms underlying this fundamental adaptation process remain poorly defined.… Click to show full abstract
Significance Unfolded protein response (UPR) is thought to coordinate cell growth and proliferation by governing endoplasmic reticulum (ER) proteostasis; however, the mechanisms underlying this fundamental adaptation process remain poorly defined. Here, by using Drosophila, mammalian models, and a human database, we uncover a dual role for Ire1/Xbp1s in development and tumorigenesis. A central element for this regulatory mechanism appears to be the association between the UPR downstream target Bip/HSPA5 and Hippo pathway transducer Yorkie (Yki)/YAP. Bip sequesters Yki in the cytoplasm to restrict its nuclear localization to impede cell proliferation, meanwhile also increasing invasive cell migration. Our results reveal an unexpected, context-dependent crosstalk between UPR and Hippo pathway in regulating tissue homeostasis and tumor progression.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
Link to full text (if available)
Share on Social Media: Sign Up to like & get
recommendations!