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IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress

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Abstract
IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface.
Keywords
Cell Biology, UNFOLDED-PROTEIN-RESPONSE, ER STRESS, MESSENGER-RNA, BINDING SITE, IRE1, XBP1, ATF6, ACTIVATION, MECHANISM, DOMAINS

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MLA
Grey, Michael J., et al. “IRE1β Negatively Regulates IRE1α Signaling in Response to Endoplasmic Reticulum Stress.” JOURNAL OF CELL BIOLOGY, vol. 219, no. 2, 2020, doi:10.1083/jcb.201904048.
APA
Grey, M. J., Cloots, E., Simpson, M. S., LeDuc, N., Serebrenik, Y. V., De Luca, H., … Lencer, W. I. (2020). IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress. JOURNAL OF CELL BIOLOGY, 219(2). https://doi.org/10.1083/jcb.201904048
Chicago author-date
Grey, Michael J., Eva Cloots, Mariska S. Simpson, Nicole LeDuc, Yevgeniy V. Serebrenik, Heidi De Luca, Delphine De Sutter, et al. 2020. “IRE1β Negatively Regulates IRE1α Signaling in Response to Endoplasmic Reticulum Stress.” JOURNAL OF CELL BIOLOGY 219 (2). https://doi.org/10.1083/jcb.201904048.
Chicago author-date (all authors)
Grey, Michael J., Eva Cloots, Mariska S. Simpson, Nicole LeDuc, Yevgeniy V. Serebrenik, Heidi De Luca, Delphine De Sutter, Phi Luong, Jay R. Thiagarajah, Adrienne W. Paton, James C. Paton, Markus A. Seeliger, Sven Eyckerman, Sophie Janssens, and Wayne I. Lencer. 2020. “IRE1β Negatively Regulates IRE1α Signaling in Response to Endoplasmic Reticulum Stress.” JOURNAL OF CELL BIOLOGY 219 (2). doi:10.1083/jcb.201904048.
Vancouver
1.
Grey MJ, Cloots E, Simpson MS, LeDuc N, Serebrenik YV, De Luca H, et al. IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress. JOURNAL OF CELL BIOLOGY. 2020;219(2).
IEEE
[1]
M. J. Grey et al., “IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress,” JOURNAL OF CELL BIOLOGY, vol. 219, no. 2, 2020.
@article{8658413,
  abstract     = {{IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface.}},
  articleno    = {{e201904048}},
  author       = {{Grey, Michael J. and Cloots, Eva and Simpson, Mariska S. and LeDuc, Nicole and Serebrenik, Yevgeniy V. and De Luca, Heidi and De Sutter, Delphine and Luong, Phi and Thiagarajah, Jay R. and Paton, Adrienne W. and Paton, James C. and Seeliger, Markus A. and Eyckerman, Sven and Janssens, Sophie and Lencer, Wayne I.}},
  issn         = {{0021-9525}},
  journal      = {{JOURNAL OF CELL BIOLOGY}},
  keywords     = {{Cell Biology,UNFOLDED-PROTEIN-RESPONSE,ER STRESS,MESSENGER-RNA,BINDING SITE,IRE1,XBP1,ATF6,ACTIVATION,MECHANISM,DOMAINS}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{22}},
  title        = {{IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress}},
  url          = {{http://doi.org/10.1083/jcb.201904048}},
  volume       = {{219}},
  year         = {{2020}},
}

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