Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response

@article{Bertolotti2000DynamicIO,
  title={Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response},
  author={A. Bertolotti and Yuhong Zhang and L. Hendershot and H. Harding and D. Ron},
  journal={Nature Cell Biology},
  year={2000},
  volume={2},
  pages={326-332}
}
PERK and IRE1 are type-I transmembrane protein kinases that reside in the endoplasmic reticulum (ER) and transmit stress signals in response to perturbation of protein folding. Here we show that the lumenal domains of these two proteins are functionally interchangeable in mediating an ER stress response and that, in unstressed cells, both lumenal domains form a stable complex with the ER chaperone BiP. Perturbation of protein folding promotes reversible dissociation of BiP from the lumenal… Expand
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TLDR
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TLDR
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TLDR
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Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins.
TLDR
The results suggest that in contrast to yeast Ire1, the regulation of mammalian IRE1alpha strongly depends on the dissociation of BiP. Expand
Stress-sensing and regulatory mechanism of the endoplasmic-stress sensors Ire1 and PERK
Abstract Ire1 and its family protein PERK are endoplasmic reticulum (ER)-stress sensors that initiate cellular responses against ER accumulation of unfolded proteins. As reviewed in this article,Expand
Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein CH1 to initiate ER stress signaling
TLDR
It is discovered that BiP is dual functional UPR sensor, sensing unfolded proteins by canonical binding to substrates and transducing this event to noncanonical, signaling interaction to Ire1 and Perk. Expand
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