Tight regulation of the unfolded protein sensor Ire1 by its intramolecularly antagonizing subdomain

Journal of Cell Science
Rubwad MathuranyanonYukio Kimata

Abstract

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) accompanies ER stress and causes the type-I transmembrane protein Ire1 (also known as ERN1) to trigger the unfolded protein response (UPR). When dimerized, the core stress-sensing region (CSSR) of Ire1 directly captures unfolded proteins and forms a high-order oligomer, leading to clustering and activation of Ire1. The CSSR is N-terminally flanked by an intrinsically disordered subdomain, which we previously named Subregion I, in Saccharomyces cerevisiae Ire1. In this study, we describe tight repression of Ire1 activity by Subregion I under conditions of no or weak stress. Weak hyperactivation of an Ire1 mutant lacking Subregion I slightly retarded growth of yeast cells cultured under unstressed conditions. Fungal Ire1 orthologs and the animal Ire1 family protein PERK (also known as EIF2AK3) carry N-terminal intrinsically disordered subdomains with a similar structure and function to that of Subregion I. Our observations presented here cumulatively indicate that Subregion I is captured by the CSSR as an unfolded protein substrate. This intramolecular subdomain interaction is likely to compromise self-association of the CSSR, explaining why Subregion I can suppr...Continue Reading

References

Jan 18, 1996·Nature·J M BergerJ C Wang
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·K MoriT Yura
Nov 3, 2004·The Journal of Cell Biology·Yukio KimataKenji Kohno
Jun 16, 2005·The Biochemical Journal·Daisuke OikawaKenji Kohno
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Joel J CredlePeter Walter
Jun 15, 2007·Nucleic Acids Research·Takashi Ishida, Kengo Kinoshita
Dec 17, 2008·Nature·Alexei V KorennykhPeter Walter
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Takao IwawakiKenji Kohno
Aug 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Han LiPeter Walter
Nov 26, 2010·Current Opinion in Cell Biology·Yukio Kimata, Kenji Kohno
Mar 30, 2011·The Journal of Cell Biology·Claudia RubioPeter Walter
Mar 30, 2011·The Journal of Cell Biology·Aditi ChawlaMaho Niwa
Feb 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Akio TsuruKenji Kohno
Feb 8, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yuki Ishiwata-KimataYukio Kimata

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Citations

Apr 8, 2016·Scientific Reports·Akio TsuruKenji Kohno
Jun 3, 2016·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuichi TsuchiyaKenji Kohno

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Methods Mentioned

BETA
protein folding
X-ray
fluorescence microscopy
transfection
two-hybrid
PCR
electrophoresis

Software Mentioned

PrDOS
GL

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