Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors

@inproceedings{Wang2012DivergentAC,
  title={Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors},
  author={Likun Wang and B. Gayani K. Perera and Sanjay B. Hari and Barun Bhhatarai and Bradley J. Backes and Markus A. Seeliger and Stephan C. Sch{\"u}rer and Scott A. Oakes and Feroz R. Papa and Dustin J Maly},
  booktitle={Nature chemical biology},
  year={2012}
}
Under endoplasmic reticulum stress, unfolded protein accumulation leads to activation of the endoplasmic reticulum transmembrane kinase/endoRNase (RNase) IRE1α. IRE1α oligomerizes, autophosphorylates and initiates splicing of XBP1 mRNA, thus triggering the unfolded protein response (UPR). Here we show that IRE1α's kinase-controlled RNase can be regulated in two distinct modes with kinase inhibitors: one class of ligands occupies IRE1α's kinase ATP-binding site to activate RNase-mediated XBP1… CONTINUE READING
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References

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The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule

  • BC Cross
  • Proc Natl Acad Sci U S A
  • 2012

Identification of an Ire 1 α endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma

  • I. Papandreou
  • Blood
  • 2011

Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma

  • I Papandreou
  • 2011

Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response

  • MM Ali
  • EMBO J
  • 2011

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