PRKCSH contributes to tumorigenesis by selective boosting of IRE1 signaling pathway
Unfolded protein response (UPR) is an adaptive mechanism that aims at restoring ER homeostasis under severe environmental stress. Malignant cells are resistant to environmental stress, which is largely due to an activated UPR. However, the molecular mechanisms by which different UPR branches are sel...
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Published in | Nature communications Vol. 10; no. 1; pp. 3185 - 16 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
18.07.2019
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Unfolded protein response (UPR) is an adaptive mechanism that aims at restoring ER homeostasis under severe environmental stress. Malignant cells are resistant to environmental stress, which is largely due to an activated UPR. However, the molecular mechanisms by which different UPR branches are selectively controlled in tumor cells are not clearly understood. Here, we provide evidence that PRKCSH, previously known as glucosidase II beta subunit, functions as a regulator for selective activation of the IRE1α branch of UPR. PRKCSH boosts ER stress–mediated autophosphorylation and oligomerization of IRE1α through mutual interaction. PRKCSH contributes to the induction of tumor-promoting factors and to tumor resistance to ER stress. Increased levels of PRKCSH in various tumor tissues are positively correlated with the expression of XBP1-target genes. Taken together, our data provide a molecular rationale for selective activation of the IRE1α branch in tumors and adaptation of tumor cells to severe environmental stress.
Cancer cells utilise the unfolded protein response (UPR) to adapt to environmental and ER stress. Here, the authors show that the glycosidase II beta subunit, PRKSCH, protects cancer cells from ER stress, by interacting with IRE1α and activating the IRE1α-XBP1 branch of the UPR. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-019-11019-w |